MEDICAL LIBRARY

The IASIC medical  library contains  peer reviewed medical literature about marijuana/ cannabis that is translated into terminology that allows for informed decision making by the general public.

About the IASIC Library

The IASIC Library is intended as a user friendly reference of the published medical literature. It is not a comprehensive review of over 2000 medical publications about cannabis and marijuana. 

The library is organized in the following manner:

  • Category – overall section content such as Allergies or Autism.
  • Summary Statement – the main science based statement in layman terminology about a medical article or articles.
  • Expanded Summary – toggle to open the summary statement to read additional information.
  • References – each statement is backed by a reference from the medical literature and most have an active link.

Definitions of Marijuana and Cannabis

Marijuana and Cannabis are used interchangeable on this web site. According to the NIH, National Institute of Health,  the word “cannabis” refers to all products derived from the plant Cannabis sativa.  The cannabis plant contains about 540 chemical substances.  The word “marijuana” refers to parts of or products from the plant Cannabis sativa that contain substantial amounts of tetrahydrocannabinol (THC). THC is the substance that’s primarily responsible for the effects of marijuana on a person’s mental state. Industrial hemp is defined as less than 0.3% dry weight THC. 

Addiction/ Cannabis Use Disorder

  • Among people age 12 or older, the percentage with a past year marijuana use disorder was 1.8% in 2002 (or 4.3 million people) and 2019 (or 4.8 million people) but showed declines in some years.

Key Substance Use and Mental Health Indicators in the United States: Results from the 2019 National Survey on Drug Use and Health. SAMHSA. Published September 2020.

  • 9% of those who experiment with marijuana will become addicted.
  • 17% of teenagers who experiment with marijuana become addicted.
  •  25-50% of daily users become addicted.

Bell CC. DSM-IV: Diagnostic and Statistical Manual of Mental Disorders. JAMA. 1994;272(10):828-29. 

  • 19.5% of lifetime users met criteria for DSM 5 Cannabis Use Disorder of whom 23% have severe symptoms and of those 48% were not functioning (not working).

Hasin DS. US Epidemiology of Cannabis Use and Associated Problems. Neuropsychopharmacology. 2018;43(1):195-212

  • This study included 24,900 surveys from the 2015 -2015 National Survey on Drug Use and Health. Mother or Father use of marijuana was associated with higher risk of substance use in adolescents and young adults living in the same household. This included increased use of marijuana, tobacco, alcohol and opioid misuse in offspring of parents who used marijuana.

Madras, BK. Et al. Associations of Parental Marijuana Use With Offspring Marijuana, Tobacco, and Alcohol Use and Opioid Misuse. JAMA. Addiction. JAMA, 2019.

  • This study is published by the National Institute of Health, NIH and the director of NIDA, the National Institute of Drug Abuse. Data from the 2018 National Survey on Drug Use and Health, NSDUH confirmed previous studies showing that the younger the age of initiation of drugs, the faster the transition to developing addiction (substance use disorder).  The prevalence of cannabis use disorder (marijuana addiction) for youth age 12 - 17 was 10.7% if using less than one year or 20.1% if using more than 3 years. The prevalence of cannabis use disorder was higher than alcohol use disorder in this age group. 

Volkow ND, Han B, Einstein EB, Compton WM. Prevalence of Substance Use Disorders by Time Since First Substance Use Among Young People in the US. JAMA Pediatr. Published online March 29, 2021. doi:10.1001/jamapediatrics.2020.6981

808 5th graders from Seattle public schools serving high crime areas were followed until age 33. Non marijuana users reported fewer symptoms of alcohol use disorder, nicotine dependence, and general anxiety disorder. Persistent, regular marijuana use in young adulthood correlated with more symptoms of cannabis use disorder, alcohol use disorder, and nicotine dependence at age 33.

 

Guttmannova, et al. The association between regular marijuana use and adult mental health outcomes. Drug Alcohol Depend. 2017;179:109-116. doi: 10.1016/j.drugalcdep.2017.06.016.

Allergies

  • Allergic disease associated with C sativa exposure and use has been reported with increased frequency, including anaphylaxis. Although relatively uncommon, allergies have been reported with increased frequency.

Ocampo TL and Rans TS. Cannabis sativa: the unconventional “weed” allergen. Ann Allergy Asthma Immunol. 2015;114(3):187-192. doi: 10.1016/j.anai.2015.01.004

Amotivational Syndrome

  • The research team found that only marijuana (but not alcohol or tobacco) intake significantly and longitudinally prompted lower initiative and persistence and provides partial support for the marijuana amotivational syndrome.

Lac A and Luk JW. Testing the Amotivational Syndrome: Marijuana Use Longitudinally Predicts Lower Self-Efficacy Even After Controlling for Demographics, Personality, and Alcohol and Cigarette Use. Prevention Science. 2018 Feb;19(2):117–126

Anxiety

  • Prospective study showing adolescent users have nearly triple the odds of an adult anxiety disorder. Although a previous systematic review examining adulthood anxiety among adolescent cannabis users reporting conflicting data on this association. (Moore et al. Cannabis use and the risk of psychotic or affective mental health outcomes: a systematic review.

Degenhardt et al. The persistence of the association between adolescent cannabis use and common mental health disorder into young adulthood. Addiction. 2013 Jan;108(1):124-33.  doi: 10.1111/j.1360-0443.2012.04015.

Autism

  • 3,080 young adult Australian twins were used to assess ADHD symptoms, autistic traits, substance use, and substance use disorders. Great ADHD symptoms and autistic traits scores were associated with elevated levels of cannabis use and cannabis use disorder.

DeAkwis D, et al. ADHD Symptoms, Autistic Traits, and Substance Use and Misuse in Adult Australian Twins. Journal of Studies on Alcohol and Drugs, March 2014.

  • This review examined the epidemiology of cannabis use among children and adolescents, including those with developmental and behavioral diagnosis. It then outlined the well-recognized neurocognitive changes shown to occur in adolescents who use cannabis regularly, highlighting the unique susceptibility of the developing adolescent brain and describing the role of the endocannabinoid system in normal neurodevelopment. They conclude that cannabis cannot be safely recommended in the treatment of developmental or behavioral disorders such as ADHD and autism spectrum disorder at this time.

Hadland SE, et al. Medical Marijuana: Review of he Science and Implication for Developmental Behavioral Pediatric Practice. J Dev Behav Pediatr. 2015.

  • Preconception cannabis use in males can have effect on subsequent generations because cannabis use is associated with widespread DNA changes in human sperm. Discs-Large Associated Protein 2 (DLGAP2), involved in synapse organization, neuronal signaling, and strongly implicated in autism, exhibited significant hypomethylation sites in human sperm.

Scrott R, et al. Cannabis use is associated with potentially heritable widespread changes in autism candidate gene GLGAP2 DNA methylation in sperm. Epigenetics. 2019.

  • Datasets from US Department of Education Individuals with Disabilities Act (IDEA), National Survey of Drug Use and Health, and CDC’s Autism and Developmental Disabilities Monitoring (ADDM) Network were investigated. Data on legal status was derived from SAMHSA. Autism Spectrum Disease (ASD) was found to be the most common form of cannabis-associated clinical tetralogy. The authors showed that medical, decriminalized and legal cannabis regies are associated with higher rates of ASD than illegal ones.

Reece AS and Hulse GK. Effect of Cannabis Legalization on US Autism Incidence and Medium Term Projections. Clinical Pediatrics. Vol 4, Iss 2, No:154

Reese SA and Hulse GK. Epidemiological Association of Various Substances and Multiple Cannabinoids with Autism in the USA. Clinical Pediatrics., Vol 4, Issue2, No: 155.

Reese SA and Hulse GK. Epidemiological Association of Various Substances and Multiple Cannabinoids with Autism in the USA. Clinical Pediatrics., Vol 4, Issue2, No: 155.

Cancer

  • A study of 369 men ages 18 – 44 between 1999-2006 showed that men with testicular germ cell tumors were more likely than controls to be current marijuana smokers. Nonseminoma and mixed histology tumors had a higher odd ratio of 2.3 for current marijuana users.

Daling JR et al. Association of marijuana use and the incidence of testicular germ cell tumors. Cancer. 2009;115(6):1215-1223.  doi: 10.1002/cncr.24159

 

  • Ever use of marijuana had a 2-fold increased risk of testicular germ cell tumor compared to never users in a study of 163 patients in LA County between 1986 – 1991. Nonseminoma and mixed histology tumors were associated with a higher 2.42 odd ratio.

Lackson JC, Carroll JD, Tuazon E, Castelao EJ, Bernstein L, Cortessis VK. Population-based case control study of recreational drug use and testis cancer risk confirms an association between marijuana use and nonseminoma risk. Cancer. 2012;118(21):5374-83.

 

  • Patients with testicular germ cell tumors have increased in the United States, 187 patients diagnosed with this cancer between 1990-1996 were more likely to be frequent marijuana users (daily or greater) than controls (odd ratio 2.2). Nonseminoma cancers had a higher odd ratio of 3.1.

Traber B, Sigurdson AJ, Sweeney AM, Strom SS, McGlynn KA. Marijuana use and testicular germ cell tumors. Cancer. 2011;117(4):848-53.  doi: 10.1002/cncr.25499.

Cannabis Hyperemesis Syndrome (Scromiting)

  • Vomiting Syndrome Discovered in Some Long-Term Marijuana Users: Researchers
    The condition has become so common, ER staff have coined a new term that helps identify it: "scromiting," for "screaming" and "vomiting."

By Wendy Fry • NBC San Diego. Published November 30, 2017 • Updated on December 8, 2017 at 2:40 pm

  • CHS, cannabis hyperemesis syndrome, occurs in patients with long term inhaled marijuana use who        present with painful abdominal pain and wrenching without other identifiable causes.

LaPoint J et al. Cannabinoid Hyperemesis Syndrome: Public Health Implications and a Novel Model Treatment Guidelines. West J Emerg Med. 2018;19(2):380-386. doi: 10.5811/westjem.2017.11.36368.

  • This is a report of a 27-year-old female and a 27-year-old man whose cause of death was attributed to CHS, cannabis hyperemesis syndrome. A third case of a 31year old man, CHS was appreciated, but not the cause of death

Nourbakhsh M, Miller A, Gofton J, Jones G, Adeagbo B. Cannabis Hyperemesis Syndrome: Reports of Fatal Cases. J Forensic Sci. 2019;64(1):270-274. doi: 10.1111/1556-4029.13819.

Cardiovascular Health

  • People with a cardiac history should not use marijuana.

A review of the literature resulted in several conclusions on marijuana and cardiac health. Patients with a history of coronary artery disease should be advised against using marijuana due to increased angina symptoms. There is a 4.8 fold increase risk of heart attack risk induced by marijuana by one study, and not verified by additional investigators.

Franz, CA and Frishman WH. Marijuana Use and Cardiovascular Disease. Cardiology in Review. 2016; 24:158-162.

  • Cannabis may be a risk factor for cardiovascular disease in young adults

This study, conducted in France, identified cannabis use as a possible risk factor for cardiovascular disease in young adults as the percentage of cannabis-related cardiovascular complications increased form 1.1% in 2006 to 3.6% in 2010.

Jouanjus E, Lapeyre-Mestre M, Micallef J. Cannabis Use: Signal of Increasing Risk of Serious Cardiovascular Disorders. Journal of the American Heart Association. 2014;3(2):np

  • A review of 52,290,927 hospitalization of patients ages 18-29 found that 1.3% were former or current cannabis users that excluded alcohol, tobacco, cocaine, and amphetamine (669,407) and the frequency of acute heart attack (0.23% vs. 0.14%), arrhythmia (4.02% vs. 2.84%), and stroke (0.33% vs. 0.26%) were higher in cannabis users as compared to non-users.

Desai, R. etal. Rising Trends in Hospitalizations for Cardiovascular Events among Young Cannabis Users (18–39 Years) without Other Substance Abuse. Medicina 2019, 55(8), 438.

  • This study found a dose-dependent relationship with increased observed heart rate of 20 -30%, with a peak effect at 10-30 minutes after marijuana exposure. The exercise threshold before the onset of angina is dramatically decreased by 48% in patients with chronic stable angina, following marijuana use.

Caldicott D, Holmes J, Roberts-Thomson K, Mahar L. Keep off the grass: marijuana use and acute cardiovascular events. European Journal of Emergency Medicine. 2005;(5):236–244.

  • This study found that the risk of critical blockage of blood flow to the heart (myocardial infarction) onset was elevated 4.8 times over baseline in the 60 minutes after marijuana use.

Mittleman A, Lewis A, Maclure B, Sherwood E, & Muller E. Triggering Myocardial Infarction by Marijuana. Circulation: Journal of the American Heart Association. 2001;103(23):2805–2809.

  • This review article summaries the World Health Organization report from 2016 and the  endocannabinoid effects on cardiovascular disease. They note that in the past decade there has been a nearly tenfold increase in the THC content or marijuana as well an increased availability of highly potent synthetic cannabinoids. These changes accompanied serious cardiovascular events, including myocardial infarction, cardiomyopathy, arrhythmias, stroke, and cardiac arrest.

Pacher P, et al. Cardiovascular effects of marijuana and synthetic cannabinoids: the good, the bad, and the ugly. Nat Rev Cardiol. 2018;15(3):151-166. doi: 10.1038/nrcardio.2017.130.

  • Cocaine and/or marijuana was found in 10% of 2,097 patients with acute MI at age < 50 and associated with a significantly higher risk of cardiovascular mortality.

 DeFillippis EM, et al. Cocaine and Marijuana Use Among Young Adults with Myocardial Infarction. J Am Coll Cardiol. 2018;1(22):2540-2551.

  • Cocaine and/or marijuana was found in 10% of 2,097 patients with acute MI at age < 50 and associated with a significantly higher risk of cardiovascular mortality.

 DeFillippis EM, et al. Cocaine and Marijuana Use Among Young Adults with Myocardial Infarction. J Am Coll Cardiol. 2018;1(22):2540-2551.

  • Researchers found that marijuana users were almost twice as likely to develop stress cardiomyopathy compared to non-users in a Nationwide Inpatient Sample of 33,343 people in the United States with stress cardiomyopathy between 2003 and 2011. Marijuana users were more likely to have a history of depression, psychosis, anxiety, alcohol use, tobacco use, and multiple substance use. 

American Heart Association News. Marijuana use may be linked to temporarily weakened heart muscle. American Heart Association. November 13, 2016.

https://www.heart.org/en/news/2018/05/01/marijuana-use-may-be-linked-to-temporarily-weakened-heart-muscle.

This national study compared 570,000 patients ages 15-54 who were admitted to the hospital between 2010-2014 for a primary diagnosis of arrhythmia (irregular heart rate). These patients were compared to 67,662,082 patients who did not have arrythmia in the hospital. Cannabis use disorder was associated with a 47%-52% increased likelihood of arrhythmia hospitalizations in the younger population. The risk of association was controlled for confounders including other substances.  Atrial fibrillation was the most prevalent arrhythmia raising concerns for stroke and other embolic events.

Patel RS, Gonzalez MD, Ajibawo T, Baweja R. Cannabis use disorder and increased risk of arrhythmia-related hospitalization in young adults. Am J Addict. 2021 Aug 25. doi: 10.1111/ajad.13215. Epub ahead of print. PMID: 34432919.

Data from 2017 and 2018 was obtained from the American Risk Factor Surveillance System survey and included 33, 173 young adults ages 18 – 44. A history of heart attack (MI – myocardial infarction) was associated with cannabis use of ore than 4 times a month, with smoking as the primary method of consumption. MI had an odd ratio of 2 times higher among cannabis users relative to non-user

Ladha KS, et al. Recent cannabis use and myocardial infarction in young adults: a cross-sectional study. CMAJ Sep 2021, 193 (35) E1377-E1384; DOI: 10.1503/cmaj.202392

 

CBD Cannabidiol

  • FDA approved the drug Epidiolex, pure CBD, for treatment in rare pediatric seizures. As part of the drug approval process, research is evaluated on the harms and benefits of the drug. The FDA issued a drug labeling warning for CBD that cautions of hepatocellular injury, or liver damage. The FDA lists CBD adverse reactions of 10% or more as somnolence, decreased appetite, diarrhea, high liver enzymes, fatigue, malaise, asthenia, rash, insomnia, sleep disorder, poor quality sleep, and infections.

            Epidiolex FDA package Label – Highlights of Prescribing Information.

  • CBD is broken down in the liver through the cytochrome P50 system. Medications that require this same type of liver metabolism when mixed with CBD can make the medication ineffective or toxic.  For example, patients on a blood thinner can have excessive bleeding in taking their medication as prescribed but also using CBD or THC.

Check your medications for interactions with CBD by entering cannabidiol in the mediation interaction checker.  Check for interactions with THC by entering cannabis.  

Drugs.com

  • 84 CBD products were analyzed from 31 companies and found that only 31% were correctly labeled.  THC was detected in 21.4% of samples up to 6.4 mg/ml. Oils were most frequently labeled correctly, at 45%.

Bonn-Miller MO. Et al. Labeling Accuracy of Cannabidiol Extracts Sold Online. JAMA.2017;318(17):1708-1709

  • A state and federal task force identified 9 product samples that contained a synthetic cannabinoid, but not CBD and eight were branded as “Yolo CBD oil,” but provided no other information about the manufacturer or ingredients. Sixty percent of individuals who used the Yolo product were seen at an emergency department.

Horth R et al. Notes from the Field: Acute Poisonings from a Synthetic Cannabinoid Sold as Cannabidiol - Utah, 2017–2018. MMWR. 2018;67(20):587-588.

Contaminants

  •  Medical marijuana obtained from dispensaries does not differ in form from recreational    marijuana. Twenty cannabis samples from legal dispensaries across northern California were found to have Cryptococcus, Mucor, Aspergillus, Gram-negative bacilli, Salmonella, Bacillus, Klebsiella and Enterobacter. The authors warm about infectious   complications in marijuana users, especially if immunocompromised.

Thompson GR et al. A microbiome assessment of medical marijuana. Clinical Microbiology and Infection. 2017;23(4):269-270.

  • A 34-year-old man presented with pulmonary aspergillosis on the 75th day after marrow transplant for chronic myelogenous leukemia. The patient had smoked marijuana heavily for several weeks prior to admission. Cultures of the marijuana revealed Aspergillus fumigatus with morphology and growth characteristics identical to the organism grown from open lung biopsy specimen. Despite aggressive antifungal therapy, the patient died with disseminated disease. Physicians should be aware of this potentially lethal complication of marijuana use in compromised hosts.

Hamadeh R, Ardehali A, Locksley RM, York MK. Fatal Aspergillosis Associated with smoking contaminated Marijuana, in A Marrow Transplant Recipient. Chest. 1988;94(2):432-433.

Depression

  • Researchers from McGill and Oxford Universities carried out systematic review andmeta-analysis that included 23,217 individuals from 11 international studies.  They found that cannabis use among adolescents is associated with significant increased risk of depression and suicidality in adulthood. The population attributable risk was found to be around 7%, which translates to more than 400,000 adolescent cases of cannabis attributed depression.

Gobbi G, Atkin T, Zytynski T et al. Association of cannabis use in adolescence and risk of depression, anxiety and suicidality in young adulthood: A systematic review and meta-analysis. JAMA. 2019;76(4):426-434. doi:10.1001/jamapsychiatry.2018.4500.

  • Prospective cohort study of 967 high school students in 4 high schools in Canada demonstrated that illicit drug use was associated with increased risk of depression, suicidal ideations and suicide attempt. Heavy cannabis use alone predicted depression, but not suicidality.

Rasic D, Weerasinghe S, Asbridge M, Langille DB. Longitudinal associations of cannabis and illicit drug use with depression, suicidal ideation and suicide attempts among Nova Scotia high school students. Drug Alcohol Depend. 2013;129(1-2):49-53.  doi: 10.

  • National Academies of Sciences, E., Health and Medicine Division, Board on Population Health and Public Health Practice, & Committee on the Health Effects of Marijuana: An Evidence Review and Research Agenda. 

Recommendations to Support and Improve the Cannabis Research Agenda.  In the Health Effects of Cannabis and Cannabinoids: The Current State of Evidence and Recommendations for Research. National Academies Press. 2017, pp 395-402. Retrieved from https://www.nap.edu/read/24625/chapter/12

Drug Interactions

  • Nearly 50% of CBD users experienced adverse drug events such as liver failure, sedation, sleep disturbance, infection and anemia. CBD is metabolized in the liver via the CYP3A4 enzyme and is therefore associated with numerous drug-drug interactions.

Brown JD. And Winterstein G. Potential Adverse Drug Events and Drug-Drug Interactions with Medical and Consumer Cannabidiol (CBD) Use. J Clinical Medicine, July 2019.

 

  • THC is metabolized in the liver utilizing the CY3A4 and CYPP2C9 enzymes which results is numerous drug-drug interactions. For example, patients given ketaconazole, a fungal treatment medication, had 27% increase in THC and 204% increase in 11-OH-THC (an active metabolite of THC). All participants in the study reported serious adverse effect when THC was combined with ketoconazole. In addition, 35% of Caucasians have genetic alterations in their CYP2C9 enzyme, meaning they cannot metabolize THC as well resulting in higher dosage of THC in their body.

Brown J. Potential Adverse Drug Events with Tetrahydrocannabinol (THC) Due to Drug -Drug Interactions. J Clinical Medicine. March 2020.

 

  • com has an ‘Interactive Checker’ where you can check your prescription medications with cannabis (marijuana) or cannabidiol (CBD). Drugs.com lists 380 drugs with known interactions with cannabis including 26 major reactions. Common drug interactions occur with medications for pain, anxiety, sleep, seizures, depression, Parkinson’s disease, blood pressure and blood thinners. Cannabidiol (CBD) has 545 drug interactions including 10 major reactions.

Drugs.com

 

Emergency Visits

  • Denver, Colorado: Between January 2012 and December 2016, there were 9973 visits to the emergency department with cannabis related diagnosis, a 3-fold increase after legalization. Of these 9.3% were due to edibles. Inhaled cannabis were more likely to be associated with cannabinoid hyperemesis syndrome and edibles were more likely to be due to acute psychiatric and cardiovascular symptoms.

Monte AA, et al. Acute Illness Associated with Cannabis Use, by Route of Exposure: An Observational Study. Annals of Internal Medicine. 2019 April 16;170(8):531-537. 

  • San Diego Marijuana Prevention Initiative 2020 Report show over 29 emergency department visits a day for cannabis and a 776% increase in primary diagnosis of cannabis illness from 2008 – 2018.

San Diego Marijuana Prevention Initiative, 2020.

  • Cannabis associated emergency department visits per 100,000 visits increased 7% monotonically annually. In the Western region visits increased from 15.4% to 26% over time. Medicare and Medicaid and uninsured patients were over 40% more likely to visit an emergency department.

Shen JJ, et al. Trends and Related Factors of Cannabis Associated Emergency Department Visits in the United States: 2006 – 2014. J Addict Med. 2019;13(3):193-200.

  • Emergency Department visits, between January 2012 through December 2016, at UC Health University of Colorado, showed 9973 visits with ICD 9 or ICD 10 code for cannabis use. Visits attributed to inhaled cannabis were more likely to be for cannabinoid hyperemesis syndrome while visits attributable to edible cannabis were more likely to be due to psychiatric symptoms, intoxication and cardiovascular symptoms.

Monte AA et al. Acute Illness Associated with Cannabis use, by route of exposure: An Observational Study. Ann Intern Med. 2019;170(8):531-537. Doi.org/ 10.7326/M18-2809

  • The energy and materials required to grow cannabis indoors was studied and quantified the corresponding greenhouse gas emissions. The analysis was performed across the United States and accounted for geographic variations in meteorological and electric grid emission data. Greenhouse gas emissions for legal cannabis ranges from 2,283 – 5,185 kg CO2-equivalent per kilogram of dried flower. Using the EPA calculator, this is equivalent to 583 gallons of gasoline consumed.

Summers, H.M., Sproul, E. & Quinn, J.C. The greenhouse gas emissions of indoor cannabis production in the United States. Nat Sustain (2021). https://doi.org/10.1038/s41893-021-00691-w

This book chapter on energy use by the indoor cannabis industry quoted energy usage calculation on indoor cannabis cultivation.

  • Cannabis consumes 1% of the nation’s energy use – the same as driving 3 million cars.
  • 1 small grow house with 10 grow lights consumes as much electricity as 10 average US homes.
  • 1 gram joint creates 10 pounds of CO2 pollution, equivalent to running 10 10-watt LED light bults for 76 hours or driving 22 miles in a 44 mph Prius.
  • Each indoor grown cannabis plant is equivalent to 70 gallons of oil.
  • Indoor cannabis consumed 20 billion kilowatt-hours of electricity annually or 15 million metric tons of CO2 released into the atmosphere each year. This is an expenditure of $6 billion per year on energy, nationally, which amounts to 9% of California household electricity use.
  • CO2 emissions by the average cannabis user is 59% of total household carbon footprint in Colorado.
  • It is estimated that cannabis energy constitutes 3% of electricity demand in parts of Washington and 0.5-1% in Colorado.

Mills, Evan and Zeramby, Scott. Energy Use by Indoor Cannabis Industry: Inconvenient Truths for Producers, Consumers, and Policymakers. The Routledge Handbook of Post-Prohibition Cannabis Research. Dominic Corva and Joshua Meisel, 2021.

IASIC Materials

Link to PDF

  • Dear Editor,
    The notion that lower opioid deaths is related to having more marijuana dispensaries is incongruent with the national opioid epidemic trends. The CDC issued its most recent overdose data recently showing yet another record in overdose deaths in 2020, up 12.5% in one year from 72,000 to 81,000. This correlates with more states expanding marijuana programs for both medical and recreational use. In some states the number of marijuana dispensaries outnumber of McDonalds and Starbucks combined.
    Colorado has had medical marijuana since 2001 and 90% of marijuana recommendations are for pain. If marijuana was an effective pain reliever, or opioid substitute, the Colorado should see decreases in drug deaths over time. However, 2019 was a record year in drug overdose deaths in Colorado, particularly prescription opioid overdoses. Based on the provisional 2020 data, Colorado will have yet another record in drug overdose deaths. Preliminarily, between 2019 and 2020 in Colorado, prescription opioid overdose deaths will be up 78%, fentanyl 110%, cocaine 44%, and methamphetamine 23%. Other states have seen similar trends.
    There is a mountain of data outlining harms associated with rampant marijuana use, normalization of drug use, and expanded marijuana programs which outstrip any real or perceived benefit. The idea that we need more marijuana stores to combat the opioid epidemic is a complete fallacy. In the midst of the COVID-19 pandemic, the is a need to "listen to the doctors and scientists" and "we need the data". Somehow, marijuana got a free pass. There is sufficient data that there are more opioid overdose deaths in those states with expanded marijuana programs and this has become a serious public health and safety concer
 
30 January 2021
Kenneth P Finn, MD
Catherine Antley, MD; Eric Voth, MD; Roneet Lev, MD
 
 

The Bradford Hill Criteria is used to prove the difference between cause and association. Once upon a time people thought tobacco and lung disease were not related. The Bradford Hill Criteria proved that tobacco causes, not just is associated with lung disease.  Similarly, applying the Bradford Hill Causation Criteria to Cannabis  is used to show that marijuana/cannabis causes chronic schizophrenia

IASIC, The International Academy on the Science and Impact of Cannabis wrote this advocacy letter IASIC Advocacy Letter as a resource for drug prevention specialists across the county.  Please feel free to use it in your work on a local and state level.

Life Expectancy

  • Habitual marijuana use among patients who had a heart attack resulted in a 29% higher death rate over the 18 years following the heart attack compared to non-users. 

Frost L, Mostofsky E, Rosenbloom JI, Mukamal KJ, Mittleman MA. Marijuana use and long-term mortality among survivors of acute myocardial infarction. American Heart Journal.2013;165(2):170–175

  • 50,373 Swedish males ages 18-19 who were part of mandatory military service were followed in a death registry up to age 60.  The results showed that ever users and heavy cannabis users (>50 times) during adolescence were associated with a higher mortality than never users.

Manrique-Garcia, et al. Cannabis, Psychosis, and Mortality: A Cohort Study of 50,373 Swedish Men. The American Journal of Psychiatry. 2016;173(8):790-798.

Marijuana Use and Dispensaries in Youth

  • A Rand corporation study of 1,887 people age 18-22 who live in Los Angeles, if they live in a neighborhood with a higher number of medical marijuana dispensaries, they use pot more frequently and have a more positive view about the drug.

Shih RA, Rodriguez A, Parast L et al. Associations Between Young Adult Marijuana Outcomes and Availability of Medical Marijuana Dispensaries and Storefront Signage. Addiction. 2019;114(1):1-22.

  • Study of 32 Oregon countries from 2006 to 2015 showed higher marijuana use by youth with higher registered marijuana patients and growers. 

Paschall MJ, Grube JW, Biglan AB. Medical Marijuana Legalization and Marijuana Use Among Youth in Oregon. J Prim Prev. 2017;38(3):329-341.

Medical Organizations Position Statements

  • The Association for Addiction Professionals does not support the use of cannabis as medicine or for recreational purposes.
  • Cannabis needs to be subject to the same research, consideration, and study as any other medicine through the FDA.

NAADAC Position Statement on the Medical and Recreational Use of Cannabis

  • Medical research does not support cannabis-based products as treatment options for the majority of neurological disorders.
  • Psychiatric and neurocognitive adverse effects have been described in recreational and medical use, which is particularly problematic in a population with compromised neurological function.
  • The interaction of cannabis products and neurological prescriptions is uncertain.

AAN Position: Use of Medical Cannabis for Neurological Disorders. American Academy of Neurology. Updated in 2020.

  • “Based on reviews by the National Eye Institute (NEI), the Institute of Medicine (IOM), and on available scientific evidence, the American Academy of Ophthalmology Complementary Therapy Task Force finds noscientific evidence demonstrating increased benefit and/or diminished risk of marijuana use in the treatment of glaucoma compared with the wide variety of pharmaceutical agents now available.”

American Academy of Ophthalmology Complementary Therapy Task Force. Marijuana in the Treatment of Glaucoma TA – 2014.

  • AAP opposes marijuana use in ages 0 – 21 due to negative effects on the developing brain.
  • AAP opposes “medical marijuana” outside the regulatory process of the US FDA
  • AAP discourages the use of marijuana by adults in the presence of minors
  • AAP strongly opposes the use of smoked marijuana because smoking is known to cause lung damage.

Committee on Substance Abuse, Committee on Adolescence. The Impact of Marijuana Policies on Youth: Clinical, Research, and Legal Update. Pediatrics. March 2015, Volume 135, Issue 3.

  • The American Cancer Society opposes the smoking or vaping of marijuana and other cannabinoids in public places because the carcinogens in marijuana smoke pose numerous health hazards to the patient and others in the patient’s presence.

American Cancer Society – Marijuana and Cancer, revised August 4, 2020

  • ACMT calls upon stakeholders to implement measures to prevent cannabis exposure in children less than 12. 

Amirshahi MM, et al. ACMT Position Statement: Addressing Pediatric Cannabis Exposure. Journal of Medical Toxicology. March 2019.

 

  • OBGYN should be discouraged from prescribing or suggesting the use of marijuana for medical purposes during preconception, pregnancy, and lactation.

Committee on Obstetric Practice. Committee Opinion No. 722 Summary: Marijuana Use During Pregnancy and Lactation. Obstetrics & Gynecology. October 2017.

The American Dental Association points out several oral health risks associated with cannabis smoking.  This includes gum disease (periodontal complications), dry mouth (xerostomia), and white plaques in the mouth (leukoplakia) as well as increased risk of mouth and neck cancers.

American Dental Association. Cannabis Oral Health Effects. August 2020.

 

  • Over 3 million Americans live with epilepsy
  • The term “medical marijuana” is a legal definition
  • Purified CBD, available by prescription as Epidiolex may be effective in treatment of Lennox-Gastaut syndrome and Dravet syndrome.
  • The purified, pharmaceutical formulation of CBD cannot be obtained from a marijuana dispensary. Products from a dispensary may not contain just CBD, but also THC, pesticides, bacteria, and other dangerous impurities.

American Epilepsy Society Position Statement on Cannabis as a Treatment for Epileptic Seizures. Feb 19, 2019.

  • Marijuana or its components are not recommended for the treatment of glaucoma due to lack of evidence, short duration of action in lowering intraocular pressure, and lack of long-term trials that evaluate the health of the optic nerve.

American Glaucoma Society Position Statement: Marijuana and the Treatment of Glaucoma

  • Patients with underlying heart disease could experience increase angina when cannabis is smoked.
  • Continual cannabis use is associated with increased risk of metabolic syndrome compared to no use.
  • The risk of stroke was higher among frequent marijuana users age 18 – 44 with concomitant e-cigarette use.
  • The public needs high quality information about cannabis, which can help counterbalance the proliferation of rumor and false claims about the health effect of cannabis products.
  • There is a need to create knowledge and automated warnings around drug-drug interactions.

Page RL, et al. Medical Marijuana, Recreational Cannabis, and Cardiovascular Health: A Scientific Statement From the American Heart Association. Circulation. 2020.

    • Smoke from marijuana combustion has the same toxins, irritants and carcinogens as tobacco smoke.
    • Marijuana smokers have a greater exposer of tar per breath than tobacco smokers.
    • Smoking marijuana clearly damages the human lung, and regular use leads to chronic bronchitis and can cause an immune-compromised person to be more susceptible to lung infections.
    • No one should be exposed to secondhand marijuana smoke. Secondhand marijuana smoke contains the same toxins and carcinogens found in directly inhaled marijuana smoke, in similar amounts if not more.
    • The American Lung Association strongly cautions the public against smoking marijuana as well as tobacco products.

American Lung Association. Marijuana and Lung Health. December 17, 2020.

  • Cannabis is a dangerous drug and as such is a serious public health concern
  • The sale of cannabis for adult use should not be legalized
  • States that have legalized cannabis for medical or adult use should be required to take steps to regulate the product and protect public health and safety

AMA Policy. Cannabis Legalization for Adult Use (commonly referred to as recreational use), 2020.

  • “There is currently no scientific evidence to support the use of cannabis as an effective treatment for any psychiatric illness. Several studies have shown that cannabis use may in fact exacerbate or hasten the onset of psychiatric illnesses, as evidence by both international trials and meta-analyses. This includes the contribution of cannabis to symptoms of mood disorders, anxiety and psychosis, particularly in young adulthood.”

Resource Document on Opposition to Cannabis as Medicine, October 2018

  • Cannabis and cannabis-derived products recommended for medical indications should be subject to FDA review and approval to ensure their safety and effectiveness.
  • Healthcare professionals should not recommend cannabis use for treatment of opioid use disorder
  • Non FDA approved cannabis recommendations by clinicians should be reported to PDMPs, Prescription Drug Monitoring Programs.

American Society of Addiction Medicine. Cannabis Policy Statement. October 10, 2020.

  • Do not prescribe currently available medicinal cannabis products to treat chronic non-cancer pain unless part of a registered clinical trial.
  • Clinical use of cannabinoid products cannot be ethically recommended outside a properly established and registered clinical trial environment.
  • Evidence of harms exist, particularly in relation to sedative effects, interactions with other medications and neuropsychiatric effects. 

https://www.choosingwisely.org.au/recommendations/fpm6

  • Review of preclinical research and clinical safety and efficacy of cannabis and cannabinoids for pain relief have identified important research gaps. Due to the lack of high-quality clinical evidence, the International Association for the Study of Pain (IASP) does not currently endorse general use of cannabis and cannabinoids for pain relief. International Association for the Study of Pain recognizes the pressing need for preclinical and clinical trials to fill the research gap, and for education on this topic.

International Association for the Study of Pain - Presidential Task Force on Cannabis and Cannabinoid Analgesia Position Statement 

 
  • Medical Society of Delaware
  • Medical Society of New Jersey
  • Medical Society of the State of New York
  • Ohio State Medical Association
  • Pennsylvania State Medical Society

            October 20, 2020:  State Medical Societies Concerned with State Government’s Efforts to Legalize Recreational Marijuana.

            Of behalf of the tens of thousands of physicians we represent, the medical societies of Delaware, New Jersey, New York, Ohio, and Pennsylvania, are again joining together to express mutually shared concerns about state governments; efforts to legalize marijuana for recreational use. Legalization continues to present serious public health concerns.

 

Medical Society of the State of New York.  State Medical Societies Concerned with State Governments’ Effort to Legalize Recreational Marijuana.

  • Marijuana can enter the fetal brain from the mother’s bloodstream.
  • THC has been found in breast milk for up to 6 days after the last recorded use.
  • Marijuana use in pregnancy is associated with adverse outcomes.
  • No one should smoke marijuana around a baby.
  • Frequent marijuana use during adolescents is associated with:
    • Changes in the brain involved in attention, memory, decision-making, and motivation
    • Impaired learning, decline in IQ, school performance and life satisfaction
    • Increased rates of school dropout and suicide attempts
    • Risk of early onset psychotic disorders such as schizophrenia
    • Greater likelihood of misusing opioids

U.S. Surgeon General’s Advisory: Marijuana Use and the Developing Brain. Created by the Office of the Surgeon General, August 2019.

Motor Vehicle Collisions

  • Cannabis is the most prevalent illicit drug identified in impaired drivers.  Epidemiological data shows risk of motor vehicle collisions increases by 2-fold after cannabis smoking. Evidence suggests recent smoking and/or blood THC concentrations 2-5 ng/mL are associated with substantial driving impairment, particularly in occasional smokers. 

Hartman RL, Huestis MA. Cannabis effects on driving skills. Clin Chem 2013; 59:478-92.

  • Recent smoking of marijuana and blood THC of 2-5 ng per milliliter are associated with substantial driving impairment. According to meta-analysis, the overall risk of involvement in an accident increases by a factor of about 2 when a person drives soon after using marijuana. In an accident culpability analysis, persons testing at 1 ng/ml of          THC or higher were 3-7 times as likely to be responsible for a motor vehicle collision. In     comparison, the risk of a vehicular collision increased by almost 5 for a driver with a        blood alcohol over 0.08%. The risk of alcohol with marijuana is associated with an increase risk than either drug alone.

Ramaekers JG, Berghaus G, van Laar M, Drummer OH. Dose related risk of motor vehicle crashes after cannabis use. Drug Alcohol Depend. 2004;73:109-19.

Neonatal Exposure

  • Using NDSUH data, cannabis use increased among pregnant women increased from 3.4% of past month use in 2002-2003 to 7% in 2016-2017. Use was higher for the first trimester than later trimesters. 2019 NSDUH data showed 5.9% of pregnant women used marijuana in the past month. 

Volkow ND, Han B, Compton WM et al. Self-reported Medical and Nonmedical Cannabis Use Among Pregnant Women in the United States. JAMA. 2019. doi:10.1001/jama.2019.7982

             

  • Marijuana use increased from 4 to 7% between 2009 and 2016 among Northern California Kaiser patients at 8 weeks gestation. 22% pregnant females less than 18 and 19% of women aged 18 - 24 tested positive for THC. Most pregnant women under report marijuana use as only, 15.9% were positive on self-reporting, 29.2% were positive on both self-report and toxicology, and most, 54.9%, were positive on toxicology only.

Young-Wolff KC, et al. Trends in Self-reported and Biochemically Tested Marijuana Use Among Pregnant Females in California 2009-2016. JAMA. 2017;318(24);2490-2491.

  • The Stillbirth Collaborative Research Network included 59 hospitals in 5 geographic areas between 2006 – 2008. Stillbirth is defined when a fetus dieds at or after 20 weeks gestation.

NIH network study documents elevated risk associated with Marijuana, other substances. December 2013.

  • A review of 24 meta-analysis studies demonstrated that women who used cannabis during pregnancy had an increased incidence of anemia. Infant exposed to cannabis in utero had a decrease in birth weight and high likelihood of needing neonatal intensive care services. 

Gunn JKL, Rosales CB, Center KE, Nunez A, Gibson SJ, Christ C, Ehiri JE. Prenatal exposure to cannabis and maternal and child health outcomes: a systematic review and meta-analysis. BMJ Open. 2016;6(4):e009986.

  • In a study of 661,617 women in Ontario Canada, cannabis use during pregnancy was        associated with significant association with risk of preterm birth.  There was a greater    frequency of small for gestational age, placental abruption, transfer to neonatal ICU, and 5-minute APGAR score of less than 4.

Corsi DJ, Walsh L, Weiss D et al. Association Between Self –reported Prenatal Cannabis Use and Maternal, Perinatal, and Neonatal Outcomes. JAMA. 2018. doi:10.1001/jama.2019.8734

  • This study shows the results of an experiment that shows that long-term, heavy use of  cannabis during pregnancy can impair fetal brain development and put the offspring at risk of neurodevelopmental disorders.

Alpar A, Di Marzo V, Harkany T. At the Tip of an Iceberg: Prenatal Marijuana and Its Possible Relation to Neuropsychiatric Outcome in the Offspring. Biol. Psychiatry. 2019;79(7):e33-45.

  • Short-term effects of cannabis use disorder, such as impairments in attention and judgment, and long-term effects, such as depression and impaired executive function, can have adverse effect on the child.

Jansson LM, Jordan CJ, Velez ML. Perinatal Marijuana Use and the Developing Child. JAMA. 2018;320(6):545-546.

  • The authors quote that approximately 10% of pregnant woman in an American study reporting using cannabis. Prenatal cannabis exposure has been found on effect children’s sleep, memory, scholastic skills, reasoning, attention, impulsivity, motivation, depression, and anxiety throughout stages of development. The authors hypothesize on the existence of “fetal cannabis spectrum disorder” based on 2-3-fold increase frequency of ADHD and autistic spectrum disorder in children and adolescents and young adult psychiatric patients who were exposed to cannabis in utero. Dr. Miriam Adelson contributed to this publication.

Schreiber S and Pick CG. Cannabis use during pregnancy: Are we on the verge of defining a “fetal cannabis spectrum disorder”? Medical Hypotheses. 2019;124:53-55.

  • Cannabis has been shown to be teratogenic (causing abnormal fetal development) in cells, animals, and humans. Particular targets of prenatal exposure include the brain, heart and blood vessels and chromosomal segregation. Cannabis used during pregnancy has been linked to congenital heart defects, gastroschisis, anencephaly, and Down syndrome.

Reese AS, Hulse GK. Explaining Contemporary Patterns of Cannabis Teratology. Clin Pediatr OA 4:146.

Neurocognitive Effects

  • This summary article by NIDA director, Dr. Nora Volkow, listed adverse effects of marijuana use based on previous studies.  Volkow notes several neurocognitive effects that include: Impaired short-term memory, impaired motor coordination, altered judgement, altered brain development, paranoia, psychosis, poor educational outcome, increased likelihood of dropping out of school, lower IQ among those who use frequently during adolescence, and decreased life satisfaction.

Volkow ND, Baler RD, Compton WM, Weiss SRB. Adverse Health Effects of Marijuana Use. N Engl J Med. 2014;310(23):2219-2227

  • A study of 1,121 adults ages 22- 36 showed that a positive urine THC was associated with worse performance in episodic memory and processing speed; Cannabis Use Disorder was associated with lower fluid intelligence

Petker T, et al. Cannabis involvement and neuropsychological performance: findings from the Human Connectome Project. J Psychiatric Neurosci. 2018. Doi:10.1503/jpn.180115.

  • This 20-year study found that persistent cannabis use was associated with neuropsychological decline broadly across domains of functioning, including IQ (declines of -0.11, -0.17, and -0.38 stand deviation units), memory, and processing speed. Cessation of cannabis use did not fully restore neuropsychological functioning.

Meier MH, Caspi A, Ambler A et al. Persistent cannabis users show neuropsychological decline from childhood to midlife. PNAS. 2012;109(40):e2657-e2664.

  • This study specifically assesses the effects of high- potency marijuana on human performance, as most studies traditionally relied on low- potency marijuana. The study suggests that high- potency marijuana consistently impairs executive function and motor control.

Ramaekers JG, Kauert G, van Ruitenbeek P, Theunissen EL, Schneider E, Moeller MR. High-Potency Marijuana Impairs Executive Function and Inhibitory Motor Control. Neuropyschopharmacology. 2006;31:2296-2303

  • Cannabis use has been shown to impair cognitive function on a number of levels from basic coordination to complex executive function task such as the ability to plan, organize, solve problems, make decision, remember, and control emotions and behavior.           

Crean RD, Crane NA, Mason BJ. An evidence-based review of acute and long term effects of cannabis use on executive cognitive function. J Addict Med. 2011;5(1):1-8. Doi.org/ 10.1097/ADM.0b013e31820c23fa.

  • Marijuana use was associated with increased impulsivity on the same day and the follow day relative to days when marijuana was not used, independent of alcohol use, in 43 participants without SUD.

Ansell EB, et al. Effects of marijuana use on impulsivity and hostility in daily life. Drug and Alcohol Dependence. 2015;148(136-142).

https://www.sciencedirect.com/science/article/abs/pii/S0376871614020092?via%3Dihub

  • MRI imaging of the brain was compared in marijuana users in Switzerland in male volunteers age 18 – 30.

Battistella G et al. Long-term effects of cannabis on brain structure. Neuropsychopharmacology. 2014;(9):2041-2048.

 

Pain and Opioids

  • This toxicology test book states that studies examining the efficacy of cannabis in the setting of induced acute pain showed no improvement. Smoked marijuana failed to attenuate thermal pain in volunteers, and an oral THC analog have no effect on postsurgical pain. Cannabinoids have some favorable outcomes when used to treat chronic neuropathic pain, although design flaws severely limit the quality of medical evidence.           

Lapoint J. Cannabinoids. In: Weitz M and Naglieri C, eds. Goldfrank’s Toxicologic Emergencies. 10th ed. China: McGraw-Hill; 2002.

  • 18 healthy women were given oral cannabis verses placebo for a sunburn pain. They had no pain relief with pot and some developed hyperalgesia, worsening pain.

Kraft B, Oral Cannabis Ineffective in Treating Acute Pain. J Anesthesia, 2008

  • 15 volunteers were given capsaicin to induce pain and the treated with either high, medium, low, or no smoke marijuana. The group with medium marijuana dose had less pain, but the group with high dose marijuana had increased pain.

Cannabis and Pain: A Clinical Review. Hill et al.  Cannabis Cannabinoid Res. 2017

  • The largest study that claims that marijuana is good for pain is based on a publication by Whiting in 2015. This publication reviewed 28 studies with 2,454 patients and compared cannabis vs placebo. They found a pain reduction in 37% of cannabis patients compared to 31% in placebo, a 6% difference. However, most of the studies that claimed improved in pain were based on neuropathic pain, not traditional pain. Furthermore, the cannabis group suffered from more serious adverse effects.                  
  • Studies that show marijuana is helpful for pain use low dose THC, low number of patients and do not balance the risks

Whiting PF, et al. Cannabinoids for Medical Use: A systematic Review and Meta-analysis. JAMA, 2015

  • 10 Advance Cancer patients were given THC pills vs placebo and reported pain relief with high doses at 15 – 20 mg. However, these same patients who claimed pain relief also became very sedated and had disorganized thoughts. They author then repeated the study and compare THC to codeine and found no difference in pain relief. 5 patients had to be excluded from the study because they developed severe anxiety after receiving THC. 

Noyles R, et al. Analgesic effect of delta-9-tetracannbinol and codeine. Clinical Pharmacology and Therapeutics. 18:84-89

Noyles R, et al. Analgesic effect of delta-9-tetracannbinol. Journal of Clinical Pharmacology, 15:139-143.

 

  • This study followed 1514 participants with chronic non-cancer pain over 4 years and found that cannabis using participants had a greater pain severity score, greater pain interference score, lower pain self-efficacy scores, and greater generalized anxiety disorder severity scores compared to those who did not use cannabis. The researchers found no evidence of temporal relationship between cannabis use and pain severity or pain interference, and no evidence that cannabis use reduced prescribed opioid use or increased rates of opioid discontinuation.

Campbell G et al. Effect of cannabis use in people with chronic non-cancer pain prescribed opioids: findings from a 4-year prospective cohort study. The Lancet Public Health. 2018;3(7):e341-e350.

  • Using marijuana during opioid treatment increases the risk that opioid treatment would be unsuccessful.

Larkin PJ, Madras BK. Opioids, overdoses, and cannabis: is marijuana an effective response to the opioid abuse epidemic? The Georgetown Journal of Law and Public Policy.

  • 371 people with long term opioid therapy were evaluated for medical cannabis use. The medical cannabis users had higher scores or risk for prescription opioid misuse, rates of hazardous alcohol use, and rates of nicotine use.

Nugent SM. Et al. Patterns and correlates of medical cannabis use of pain among patients prescribed long term opioid therapy. Gen Hosp Psychiatry 2018.

  • The book Marijuana as Medicine? The Science Beyond the Controversy reviews several studies on cannabis and pain and finds significant harms with inconsistent benefit.

Marijuana as Medicine? The Science Beyond the Controversy. Alison Mack, Janet Joy.

  • The authors of this article conclude that the unsettling safety profile of cannabis, the lack of strong empirical support for its efficacy, the general absence of CBD in what is used “medically,” and the methodological challenges in conducting research suggest that, at present, cannabis should not necessarily be considered an optimal choice as a drug for pain management

Cannabis for Chronic Pain: Not Ready for Prime Time. Carr and Schatman. Am J Public Health

  • This large study used the National Survey on Drug Use and Health, NSDUH, data from 2015 and found that medical marijuana users were significantly more likely to report medical use of prescription drugs and more likely to report nonmedical use of prescription drugs in the past 12 months of any prescription drug.

Caputi L, Humphreys L. Medical Marijuana Users are More Likely to Use Prescription Drugs Medically and Nonmedically. Journal of Addiction Medicine. 2008;12(4):295–299.

  • This study of 209 patients between 2011 and 2014 found that participants with cannabis in their initial urine drug toxicology were more likely to have a future occurrence of an opioid misuse, have a history of substance abuse, and more likely to have a future occurrence of an opioid related aberrancy. 

Dibenedetto D, Weed V, Wawrzyniak K, Finkelman M, Paolini J, Schatman M, Kulich R. The Association Between Cannabis Use and Aberrant Behaviors During Chronic Opioid Therapy for Chronic Pain. Pain Medicine. 2017;19(10):1997-2008.

  • A PubMed review of 2,237 titles resulted in 14 studies that met inclusion criteria to review and found cannabis use ranging 6.2 – 38% in chronic opioid users compared to 5.8% in general population. Cannabis use in chronic opioid patients shoed statistically significant associations with present and future aberrant opioid-related behaviors.

Reisfield GM et al. The Prevalence and Significance of Cannabis Use in Patients Prescribed Chronic Opioid Therapy: A Review of the Extant Literature. Pain Med. 2009;(8):1434-41.

  • Data from 34,653 participants from the National Epidemiologic Survey on Alcohol and Related Conditions, from 2001-2002 compared to 2004-2005, showed that cannabis use increased the risk of developing nonmedical prescription opioid use and opioid use disorder.      

Olfson M, Wall M, Liu S, Blanco C. Cannabis Use and Risk of Prescription Opioid Use Disorder in the United States. American Journal of Psychiatry. 2017;175(1):47–53.

  • This study debunks bad science published by Bauchheber et all in JAMA where they found that from 1999-2010 states with medical cannabis laws experienced slower increases in opioid analgesic overdose mortality. They claimed that medical marijuana laws were protective in opioid overdoses. However, the study used data before legalization was expanded. When the same exact study was repeated extending the data from 1999 – 2017, the results showed the opposite association from the initial flawed study. States passing a medical cannabis law experienced a 22.7% increase in overdose deaths.

Shover CL, Davis CS, Gordon SC, Humphreys K. Association between medical cannabis laws and opioid overdose mortality has reversed over time. PNAS. 2019;116(26):12624-12626.

  • Bleyer debunks the “marijuana protection hypothesis.” He evaluated opioid mortality in all states and the District of Columbia through 2017 and showed that the 23 legalizing states had a 78% statistically significant acceleration of opioid death rates after medical or recreational legalization.

Bleyer, A and Barnes, B. Contribution of Marijuana Legalization to the U.S. Opioid Mortality Epidemic: Individual and Combined Experience of 27 States and District of Columbia.

  • Hsu and Kovacs published bad science in the British Medical Journal in 2021 claiming that increased number of cannabis store fronts correlates with decreased opioid deaths in that county zip code in the 23 states that have legalized marijuana. While the study showed nice graphs and calculations, they failure to zoom out to the big picture of what is happening in the total state and compare to all the states.
  • The American Society of Addiction Medicine, ASAM, states that cannabis should not be used to treat opioid use disorder.  This follows the studies that show increased misuse of opioids without improvement of pain in people who use cannabis.

American Society of Addiction Medicine. Cannabis Policy Statement. October 10, 2020.

  • Systemic review and meta-analysis of six randomized controlled trials included 1442 participants with cancer related pain and low risk of bias. The studies showed no difference between cannabinoids and placebo in pain scores. Cannabinoids had a higher risk of adverse events when compared to placebo, especially dizziness and somnolence.  

Boland EG, Bennett MI, Allgar V, Boland JW. Cannabinoids for adult cancer-related pain: systematic review and meta-analysis. BMJ Support Palliat Care. 2020 Mar;10(1):14-24. doi: 10.1136/bmjspcare-2019-002032. Epub 2020 Jan 20. PMID: 31959586.

  • 26 adolescent/young adults ages 14 – 22 met the criteria of opioid use disorder and used marijuana to get and high and a belief that smoking marijuana will help them not return to opiate use. In all cases, marijuana use failed to stop opioid addiction and facilitated their return to heavy opioid use.

 

Steven L. Jaffe. Case Reports on the Failure of Smoking Marijuana to Prevent Relapse to Use of Opiates in Adolescents/Young Adults With Opiate Use Disorder.

Emerging Trends in Drugs, Addictions, and Health, Volume 1,2021. 100011,ISSN 2667-1182,

https://doi.org/10.1016/j.etdah.2021.100011.

  • Lack of Science
  • Increased Opioid Use
  • Addiction
  • Withdrawal
  • Risk/Benefit Calculation

Lev, Roneet. Pain and Pot presentation to the Prevention Technology Transfer Center, March 10, 2021

Pancreatitis

  • Cannabis has been increasingly implicated as a cause of acute pancreatitis. Pancreatitis is inflammation of the pancreas that results in severe abdominal pain. It can be caused by alcohol, gallstones, various drugs, infections, and other conditions. Pancreatitis caused by cannabis was first reported in the medical literature in 2004, and since there have been multiple cases described.

Singh, Rohit MD; Torre, Kristin MD; Saba, Marian MD; Stepczynski, Jadwiga MD Cannabis-induced Pancreatitis, Pancreas: August 2020 - Volume 49 - Issue 7 - p e66-e67

doi: 10.1097/MPA.0000000000001605

Pediatric Exposures

  • Children age 10 or less were evaluated for marijuana exposure between 2009 and 2015 with 81 children treated at the children’s hospital and 163 consulted at the regional poison center. The median age of the children was 2. The annual poison center calls for child marijuana exposure increased 5-fold since legalization I the state. Edibles were responsible for 52% of the exposures.

Wang GS et al. Unintentional Pediatric Exposures to Marijuana in Colorado, 2009-2015.

  • One in six toddlers between the age of one month and 2 years who were admitted to Children’s Hospital Colorado between January 2013 and April 2014 with bronchitis, tested positive for THC metabolites. Positive marijuana exposure in the toddlers went up to 21% post legalization from 10% before legalization.                       

American Academy of Pediatrics. "One in six children hospitalized for lung inflammation positive for marijuana exposure: Few states where marijuana use is legal restrict its use around children." ScienceDaily. ScienceDaily, 30 April 2016. 

  • Urine samples were obtained from children who were hospitalized in Colorado and had a parent participating in a smoking cessation study. All children ahd urine samples that were analyzed for cotine (tobacco metabolize) and 11-hydroxy-delta9-tetrahydrocannabinol (COOH-THC, a marijuana metabolite.) Approximately half of the children in the study had biological evidence of exposure to marijuana.

Wilson KM, et al. Marijuana and Tobacco Coexposure in Hospitalized Children.

Psychosis

Several large prospective studies have followed teens through young adulthood, during the age of risk for using marijuana and for developing psychosis, in order to address the question of which behavior comes first.  Out of five studies, one found a bidirectional effect and four determined that marijuana use significantly increased risk for subsequent psychosis, not vice-versa.  

  • This study followed 6354 kids from age 15-16 until age 30. The authors concluded that the risk of developing psychosis was increased in individuals who tried cannabis 5 times or move. This increased risk was considered significant and adjusted for other risks such as parental psychosis, substance use, and more. 

"Mustonen A, Niemelä S, Nordström T, Murray GK, Mäki P, Jääskeläinen E, Miettunen J. Adolescent cannabis use, baseline prodromal symptoms and the risk of psychosis. Br J Psychiatry. 2018 Apr;212(4):227-233. doi: 10.1192/bjp.2017.52. PMID: 29557758.

  • The study followed 3,720 Canadian students ages 13 to 16 and found that psychosis symptoms at age 15 had a statistically significant positive association with cannabis use at age 16.

Bourque J, Afzali M, & Conrod P. Association of Cannabis Use With Adolescent Psychotic Symptoms. JAMA Psychiatry. 2018;75(8):864–866.

  • This publication is a meta-analysis that evaluated 30 different studies of healthy controls and people at ultra-high-risk for psychosis (UHR), and showed that UHR cannabis users had higher rates than nonusers of positive psychotic symptoms.

Carney R. et al. Cannabis use and symptom severity in individuals at high risk for psychosis: a meta-analysis.

  • For this study, a systematic review was conducted of studies that investigated the association between cannabis consumption and psychosis. They included 18 studies and 66,816 individuals. The study found that higher levels of cannabis use increased the risk of psychotic outcomes by an odd ratio of 3.9 and confirmed a dose-response relationship between the level of use and the risk for psychosis.

Marconi A, Di Forti M, Lewis C, Murray R and Vassos E. Meta-analysis of the Association Between the Level of Cannabis Use and Risk of Psychosis. Schizophrenia Bulletin. 2017;42(5):1262–1269.     

  • This publication reviewed 35 studies from 4804 references and revealed an increase in risk of psychosis of about 40% in participants who had ever used cannabis, and a 50-200% increase in risk for participants who used most heavily. The studies analyzed included the lower potency marijuana from previous years. 

Moore, T., Zammit, S., Lingford-Hughes, A., & Barnes, T. Cannabis use and risk of psychotic or affective mental health outcomes: a systematic review. The Lancet. 2007;370(9584), 319–328.

  • This study is based on a study from Finland in 18,478 patients. Cannabis induced psychosis resulted in 46% 8-year risk of schizophrenia spectrum diagnosis. For amphetamine induced psychosis the risk was 30%. 

Niemi-Pynttari JA, et al. Substance Induced Psychosis Converting into Schizophrenia: A Register Based Study of 18,478 Finnish Inpatient Cases. J Clin Psychiatry 2013; 74(1):394-e99.

  • This study compared 901 adult patients with first episode of psychosis across 11 sites with 1237 population controls and found that daily cannabis use was associated with increased odds of psychotic disorder compared with never users, increasing to nearly 5 times increased odds for daily use of high potency types of cannabis. The percent of cases of psychosis in each site would have been lower if cannabis was avoided.

Di Forti M et al. The contribution of cannabis use to variation in the incidence of psychotic disorders across Europe (EU-GEI): a multicenter case control study. Lancet Psychiatry. 2019;6(5):427-436.  doi: 10.1016/S2215-0366(19)30048-3.

  • Prospective epidemiological studies have consistently demonstrated that cannabis use is associated with an increased subsequent risk of both psychotic symptoms and schizophrenia-like psychosis. Early onset of use, daily use of high potency cannabis, and synthetic cannabinoids carry the greatest risk. Functional MRI studies have linked the psychomimetic and cognitive effects of THC on areas of the brain implicated in psychosis.

Murray RM et al. Cannabis-associated psychosis: Neural substrate and clinical impact. Neuropyschopharmacology. 2017;124:89-104. doi: 10.1016/j.neuropharm.2017.06.018

  • The ABCD Study, Adolescent Brain Cognitive Development, is the largest long-term study of brain development and child health in the United State. The study includes 21 research sites across the United States who invited 11,878 children ages 9-10 to join the study and follow through young adulthood.

This study used the ABCD data on 4361 children age 8.9- to 11-year-old and found that offspring psychosis increased when the mother continued to use cannabis after she knew she was pregnant.

Fine JD et al. Association of Prenatal Cannabis With Psychosis Proneness Among Children in the Adolescent Brain Cognition Development (ABCD) Study. JAMA Psychiatry. 2019;76(7):762-764.

The Bradford Hill elements of causation illustrate a causal relationship between the use of marijuana and the development of psychosis.  As seen for other agents associated with disease outcomes,  the Bradford Hill analysis has been essential to our understanding. There was a time when physicians did not realize that smoking tobacco and developing lung cancer were related in a causal sense, and applying the Bradford Hill analysis to the epidemiology of lung cancer revealed the causal association.  You will find the corresponding analysis for marijuana and psychosis here.

PTSD

  • From 1992 – 2011, 2276 veterans with PTSD were admitted to specialized VA treatment programs. At 4 months after discharge from the program subjects who started using marijuana had increased PTSD symptoms at a scale of +0.34, while those who stopped marijuana had a decrease of symptoms at a scale of -0.18. Initiating marijuana use after treatment was associated with worse PTSD symptoms, more violent behavior, and alcohol use. The authors concluded that marijuana appears to worsen PTSD symptoms and nullify the benefits of specialized intensive treatment. Cessation or prevention is an important goal of treatment.

Wilkinson ST, Stefanovics E, Rosenheck RA. Marijuana use is associated with worse outcomes in symptom severity and violent behavior in patients with posttraumatic stress disorder. J Clin Psychiatry. 2015 Sep;76(9):1174-80. doi: 10.4088/JCP.14m09475. PMID:

 

  • 790 US Veterans completed a study on PTSD symptoms, substance use and marijuana use. Participants who had PTSD symptoms were more likely to be using marijuana and synthetic cannabis in their lifetimes and in the past month. Those with PTSD symptoms and marijuana use where more likely to expect marijuana to assist with relaxation and tension reduction.

Grant S, Pedersen ER, Neighbors C. Associations of Posttraumatic Stress Disorder Symptoms With Marijuana and Synthetic Cannabis Use Among Young Adult U.S. Veterans: A Pilot Investigation. J Stud Alcohol Drugs. 2016 May;77(3):509-14. doi: 10.15288/jsad.201

 

  • In a study of 200 men and women with chronic PTSD, individual who were using cannabis or other drugs were found to have a higher risk for not completing PTSD treatment and had prolonged cycle of PTSD and substance use.

Bedard-Gilligan M, Garcia N, Zoellner LA, Feeny NC. Alcohol, cannabis, and other drug use: Engagement and outcome in PTSD treatment. Psychol Addict Behav. 2018 May;32(3):277-288. doi: 10.1037/adb0000355. Epub 2018 Mar 29. PMID: 29595297.

Public Health

  • The medical and scientific community have set criteria of what constitutes a medicine.  We now have a system where politicians not doctors can decide what a medicine is.  Standard Criteria for marijuana to be considered a medicine include:
  • The chemistry of the drug must be known and reproducible
  • Adequate safety studies much have been done
  • Adequate and well controlled studies must have proven the efficacy of the drug
  • The drug must be accepted by qualified experts
  • The scientific evidence must be widely available

These criteria have not been met of the marijuana plant or the numerous cannabis-based products.

Voth EA. And Schwartz RS. Medical Applications of Delta-9-Tetrahydrocannabinol and Marijuana. Annals of Internal Medicine. Vol 126; No 10, 1997.

  • Bypassing the usual safety and efficacy process of the FDA is a dangerous and unnecessary precedent which widely enhances the availability and acceptance of marijuana. 

Voth, EA. A Peek into Pandora’s Box: The Medical Excuse Marijuana Controversy. Journal of Addictive Diseases. Vol 22, No 4, 2003.

Cannabis is the most widely illegal drug in Ireland with 8% of adults reporting some use in the past year and the most likely substance to cause people under the age of 25 to seek addiction treatment. The authors warn of the slippery slope where politicians bypass the Health Product Regulatory Authority in determining what is and what is not a medicine. Despite the lack of scientific evidence for efficacy, chronic pain is by far the most common reason for dispensing of cannabis despite the lack of scientific evidence.

Smyth, B.P., Cannon, M. Cannabis and public health—a need to reclaim the narrative. Ir J Med Sci (2021). https://doi.org/10.1007/s11845-021-02570-x

Cannabis use is increasing among young adults, but its effects on cardiovascular health are poorly understood. We aimed to assess the association between recent cannabis use and history of myocardial infarction (MI) in young adults (aged 18–44 yr).

 

Karim S. Ladha, Nikhil Mistry, Duminda N. Wijeysundera, Hance Clarke, Subodh Verma, Gregory M.T. Hare and C. David Mazer
CMAJ September 07, 2021 193 (35) E1377-E1384; DOI: https://doi.org/10.1503/cmaj.202392

Pulmonary Health

  • This 40-year study found that heavy cannabis smoking was significantly associated with more than a twofold risk of developing lung cancer.

Callaghan R, Allebeck P, and Sidorchuk A. Marijuana use and risk of lung cancer: a 40-year cohort study. Cancer Causes & Control. 2013;24(10):1811–1820.

  • This study of 14,798 adolescents age 12 -17 showed that respiratory symptoms such as wheezing was 2 times higher among those who used cannabis in vaping devises (ENDS – electronic nicotine delivery systems), more than those who used either e-cigarettes or regular cigarettes.

 Boyd CJ, et al. Cannabis, Vaping, and Respiratory Symptoms in a Probability Sample of U.S. Youth. J of Adolescent Health. March 2021.

  • Pollution levels as fine particulate matter in the air and how long they persistent was compared with marijuana joint, the bong with its bowl, the glass pipe, electronic vaping pen, and a Marlboro cigarette inn 60 controlled experiments. Cannabis joints were the most polluting – 3.5 times that of a Marlboro. The emission rate for a cannabis bong was 67% that of a joint; the glass pipe’s emission rate was 54% of the joint, and the vaping pen’s emission rate was 44% of the joint, as polluting as a cigarette, but hung around longer.

 

Wayne R. Ott, Tongke Zhao, Kai-Chung Cheng, Lance A. Wallace, Lynn M. Hildemann,

Measuring indoor fine particle concentrations, emission rates, and decay rates from cannabis use in a residence, Atmospheric Environment: X, Volume 10, 2021,100106,ISSN 2590-1621,https://doi.org/10.1016/j.aeaoa.2021.100106.

Schizophrenia

Schizophrenia is a serious mental health disorder of misinterpretation of reality. Symptoms include hallucinations, delusions, and disordered thinking and behavior. Psychosis (see different library section) is a symptom to being out of touch with reality such as hallucinations, delusions, and disordered thinking. Schizophrenia is a DSM V disorder, while psychosis is a symptom not a disease.

  •  A study in Demark studied 7,186,834 individuals 16 year and older from 1972 to 2016 and evaluated all people who required psychiatric service for cannabis use or schizophrenia. Cannabis use disorder increased the risk of developing schizophrenia later by 5-fold. This means the adjusted hazard ratio for developing schizophrenia is 5.  The population attributable risk factor (PARF) explains the risk of a disease caused by an offending agent. For example, if no one smoke tobacco we would prevent 90% of lung cancer cases.  The PARF for schizophrenia caused by cannabis increased from 2% in the 1970s and 1980s to 8% in 2016.   This is a 7-fold increase in schizophrenia attributed to cannabis over time. The author states that “Cannabis is not a safe drug.”

Hjorthøj C, Posselt CM, Nordentoft M. Development Over Time of the Population-Attributable Risk Fraction for Cannabis Use Disorder in Schizophrenia in Denmark. JAMA Psychiatry. Published online July 21, 2021. doi:10.1001/jamapsychiatry.2021.1471

Seizures

  • Synthetic marijuana, also known as “Spice” is a chemical produced in a lab with similar structure to THC. Spice does not show up on drug screens.  It is a well established cause of seizures.

de Havenon A, Chin B, Thomas KC, Afra P. The secret "spice": an undetectable toxic cause of seizure. Neurohospitalist. 2011;1(4):182-186. doi:10.1177/1941874411417977

 

  • Natural cannabinoid delta-9-THC 10mg/kg and synthetic cannabinoid JWH-018 (spice) triggered electrographic seizures in mice.

Malyshevskaya, O., Aritake, K., Kaushik, M.K. et al. Natural (∆9-THC) and synthetic (JWH-018) cannabinoids induce seizures by acting through the cannabinoid CB1 receptor. Sci Rep 7, 10516 (2017). https://doi.org/10.1038/s41598-017-10447-2

Suicide

  • This study examined NSDUH (National Surveys on Drug Use and Health) data from 281,650 adults ages 18 – 34 between January 2008 and December 2019 and noted an increase of 40% to 60% in suicidal ideation, plan and attempt associated with cannabis use and major depression.

Han B, Compton WM, Einstein EB, Volkow ND. Associations of Suicidality Trends With Cannabis Use as a Function of Sex and Depression Status. JAMA Netw Open. 2021;4(6):e2113025. doi:10.1001/jamanetworkopen.2021.13025

 

  • This study was conducted from a registry of 13,986 twins from Australia. A monozygotic (Identical) twin who use cannabis frequently was more likely to report suicidal ideations compare to their identical twin who used cannabis less frequently, even after adjustment for other variants. There the increased likelihood of suicidal ideation in frequent cannabis users cannot be solely attribute to common predisposing factors.

Agrawal A, Nelson EC, Bucholz KK, Tillman R, Grucza RA, Statham DJ, Madden PA, Martin NG, Heath AC, Lynskey MT. Major depressive disorder, suicidal thoughts and behaviours, and cannabis involvement in discordant twins: a retrospective cohort study. Lancet

 

  • This study involved 6445 individuals who received treatment for cannabis use disorder in Denmark and determined a higher mortality rate than the general population. The most common cause of death was accidents. Suicide occurred 5 times more frequently than a control population and homicides occurrent 4 times as often.

Arendt M, Munk-Jørgensen P, Sher L, Jensen SO. Mortality following treatment for cannabis use disorders: predictors and causes. J Subst Abuse Treat. 2013 Apr;44(4):400-6. doi: 10.1016/j.jsat.2012.09.007. Epub 2012 Nov 2. PMID: 23122774.

 

  • This study evaluated 743 adolescents for psychopathology. They compared adolescents with suicidal ideations to a control population. This study showed that any use of cannabis in early adolescent period is a strong independent predictor of attempted suicide in young adulthood.

Clarke MC, Coughlan H, Harley M, et al. The impact of adolescent cannabis use, mood disorder and lack of education on attempted suicide in young adulthood. World Psychiatry. 2014;13(3):322-323. doi:10.1002/wps.20170

 

  • This study included long running longitudinal data from Australia to New Zealand that followed 3765 participants from age 17 until 30. They recorded clear and consistent associations and dose-response relations between frequent adolescent cannabis use and all adverse young adult outcomes including suicide attempt.

Silins E, Horwood LJ, Patton GC, Fergusson DM, Olsson CA, Hutchinson DM, Spry E, Toumbourou JW, Degenhardt L, Swift W, Coffey C, Tait RJ, Letcher P, Copeland J, Mattick RP; Cannabis Cohorts Research Consortium. Young adult sequelae of adolescent cannabis

  • Completed suicides in Colorado have increased steadily from 2004 to 2018. Marijuana was present in 12.8% of all 14,229 suicides. For all ages, alcohol was the leading cause of drug found on death at 35.5%. However, for ages 10 –  19, marijuana was the leading drug found in 19.8% or 943 completed suicides, surpassing alcohol at 12.8%. 

 The Colorado Center for Health and Environmental Data, Department of Public Health and Environment.

269 adolescent suicide cases in Colorado were analyzed. Marijuana was found in 16.1% of adolescent suicide cases (age 10-19) compared with 6.9% of adults. Marijuana was found more than alcohol (12.7%) on toxicology results.

 

Jamison E, Bui AG, Herndon K, Bol K. Adolescent suicide in Colorado, 2008-2012. 2014 Nov;94:1-8.

https://www.colorado.gov/pacific/sites/default/files/CHED_VS_Health-Watch-No-94-Adolescent-Suicide-in-Colorado-2008-2012_0817.pdf

  • This cohort study evaluated health insurance claims data from 75,395,344 beneficiaries between 2003 and 2017, finding that rates of self harm injuries among males younger than 40 years increased more in states legalizing recreational cannabis dispensaries compared to states without legalization.

Matthay, EC. Et al. Evaluation of State Cannabis Laws and Rates of Self-harm and Assault. JAMA Network Open. March 2021.

Violence

  • Consistent marijuana use was related to an increased risk of intimate partner violence in a longitudinal study of 9,421 subjects ages 15 – 26. Consistent marijuana use, particularly consistent use throughout adolescence, is associated with perpetration or both perpetration of and victimization by intimate partner violence in early adulthood. Marijuana use should be considered as a target of early intimate partner violence intervention and treatment programming.

Reingle JM, et al. The Relationship Between Marijuana Use and Intimate Partner Violence in a Nationally Representative, Longitudinal Sample. Journal of Interpersonal Violence. 2012;27(8) 1562-1578. DOI:10.1177/0886260511425787.

  • 296,815 adolescents and young adults were included in 30 studied. Evidence showed that the risk of violence was higher for persistent heavy users compared with past-year users and lifetime users. The results showed a significant association of cannabis use and physical violence even with adjustment for socioeconomics and other substance use.

Dellazizzo L, Potvin S, Dou BY, Beaudoin M, Luigi M, Giguère CÉ, Dumais A. Association Between the Use of Cannabis and Physical Violence in Youths: A Meta-Analytical Investigation. Am J Psychiatry. 2020 Jul 1;177(7):619-626. doi: 10.1176/appi.ajp.2020.191

 

Withdrawal from Cannabis

  • Symptoms of marijuana withdrawal include: anxiety, diminished appetite, mood changes, irritability, sleep difficulties, including insomnia, headaches, loss of focus, cravings for marijuana, sweating, including cold sweats, chills, increased feelings of depression, stomach problems.  These symptoms can range from mild to more severe, and they vary from person to person. These symptoms may not be severe or dangerous, but they can be unpleasant. The longer someone uses marijuana, the more likely they are to experience withdrawal symptoms. 

Hasin DS. US Epidemiology of Cannabis Use and Associated Problems. Neuropsychopharmacology. 2018;43(1):195-212.

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