HIGH-POTENCY THC CONCENTRATED CANNABIS PRODUCTS ARE NOT MEDICINE

In November 2000, Colorado voters passed Amendment 20, which legalized medical use of marijuana for debilitating medical conditions, effective June 2001. Initially, use remained somewhat limited until 2009 when the US Department of Justice issued the 2009 Ogden memo¹, and the Colorado Legislature established the Colorado Medical Marijuana Code in 2010 allowing for the legal licensing of medical marijuana businesses. Concentrated marijuana products began to appear in the market in 2010. In 2009 there were 5,000 people on the medical marijuana registry, in 2011 there were 119,000 people. Then, in November 2012, Colorado passed Amendment 64, which legalized retail sales of marijuana. Personal use was legalized on December 10, 2012, after the Governor certified the election results. Dispensary doors opened in 2014.

The Colorado Experiment

In the two decades since Colorado legalized medical marijuana, Tetrahydrocannabinol (THC) potency, the most psychoactive component in cannabis, significantly increased in marijuana products. While the marijuana available in the 1960s and 1970s had an average THC content of less than 2%, a study of the changes in cannabis potency from 1995-2014 by the University of Mississippi, found that the THC percentage in illicit cannabis products seized by the DEA, averaged 4% in 1995 and 12% in 2014.² As the earliest state to legalize marijuana, Colorado could have led policy development in this area in order to best protect public health, but sadly that has not happened.

• In 2023, in Colorado, the average potency in the plant is 20% THC with strains that are much higher and concentrated hash oil products such as wax, shatter, dab, average 69% THC but can reach upward of 99.9% pure THC.
• Currently in Colorado 18-20-year-olds with a medical marijuana card can purchase 2 grams of concentrate every day. Adults 21 and older can purchase 8 grams of concentrates every day.
• Prior to the passage of HB21-1317, which passed almost unanimously with bipartisan support, anyone could purchase 40 grams of concentrates per day, even those 18-20 with a medical card.
• Consider this, if a one-gram bag of shatter is 80% THC, then that is 800 mg of THC, or 1,600 mg THC per day for 18-20-year-olds and 6,400 mg THC for adults. Compare this with the FDA approved THC based medication dronabinol (Marinol) where the maximum recommended dose is 20 mg per day.

Limited Research on Marijuana for Medical Conditions

Research on the benefits of marijuana for medical conditions from the United States and around the world is limited to THC potency of less than 10%. This can be in part because research is difficult since it is a DEA Schedule 1 drug — Schedule I drugs, substances, or chemicals are defined as drugs with no currently accepted medical use and a high potential for abuse — but also because levels of THC higher than this put people at risk for possible consequences, including psychosis. As a result, Institutional Review Boards (IRBs) may not approve randomized, double-blind, placebo-controlled trials of high potency THC marijuana, even if the DEA scheduling were to change.

Several large systematic reviews and meta-analyses of peer reviewed studies of cannabis for medical conditions done to date used THC percentages at or below 10%.^3-5 There are no controlled studies of the highly concentrated cannabis products such as vaping hash oil, smoking shatter, wax, or dab for any medical condition. To put this in perspective, several of the pain studies in the systematic reviews demonstrating benefits utilized the pharmaceutical drug Sativex which is an oral mucosal spray with 2.7 mg THC and 2.5 mg CBD per dose. A typical marijuana joint weighs 0.5 g. If the product is 12 – 23% THC then a typical joint contains 60 – 115 mg of THC which is 20 – 40 times the medicinal dose.

The Inverse Relationship between Cannabis Potency and Pain Relief

A recent analysis of cannabis potency in medical and recreational programs in the United States found the average concentration of THC in all states was two to three times the THC content known to be efficacious in the treatment of pain (i.e. >5–10%) and that a vast majority of products in all states, including medical-only programs, contained THC designed for recreational use (i.e. > 15%).⁶  In Colorado, they found that most products available in medical dispensaries have greater than 15% THC.

The authors point out that patients who find this information in their online searches may subsequently believe high potency products are suitable for medical purposes, placing themselves at higher risk of cannabis intoxication. This is especially concerning in light of the systematic review and meta-analysis of 15 studies of psychiatric symptoms caused by cannabis constituents.⁷ The authors found that acute administration of THC induces significant increases in positive, negative, and other symptoms associated with schizophrenia and other mental disorders with large effect sizes in adults with no history of psychotic or other major psychiatric disorders.

In the early studies of smoked cannabis for pain, a cannabis naïve participant had a psychotic response to the study cigarette which was 3.56% THC.⁸ As a result, subsequent cannabis studies have excluded participants without prior experience smoking cannabis which makes it difficult to have double-blinded studies. There have been several studies that support the use of smoked cannabis for neuropathic pain, however the dose of THC in all these studies has been under 10%.^8-10 In fact, a study in healthy volunteers on the effects of cannabis on capsaicin-induced pain found that there is a window of modest analgesia for smoked cannabis, with 2% THC providing no benefit, 4% THC providing significant decrease in pain but 8% THC resulting in an increase in pain or hyperalgesia.¹¹

This has been further supported by a recent study of 989 adults who used cannabis every day for chronic pain.¹² The authors found that high frequency medical marijuana use, especially the higher potency THC products, was associated with worse pain among individuals with chronic pain while those who used less frequently and primarily cannabidiol (CBD) and non-inhalation administration routes had better outcomes. This is important because the primary reason people report purchasing medical marijuana in Colorado is for chronic pain issues.¹³ It is also important because, without any regulation on the THC content, medical marijuana products available in Colorado are no different than recreational products where there has yet to be any limits placed on THC potency or any meaningful limits on product types permitted to be sold.

Consequently, people are using high potency THC marijuana that may actually increase their level of pain. Research from other countries provides the best source of information on the consequences of high potency THC. There is an increasing body of literature that indicates psychotic symptoms can result from the use of high potency THC products. Other literature exposes the link between addiction, depression, anxiety, violence, and suicide and regular cannabis use. Cannabis use can impair the ability to make an accurate psychiatric diagnosis and can affect the medications often used for treatment.  

Why Limits on Cannabis THC Potency are Necessary

Research indicates there are seven risks that create compelling reasons to limit high-potency THC:

1. Increased risk of addiction
2. Increased risk of psychosis
3. Increased risk of violent behavior
4. Increased risk of suicide
5. Increased risk of PTSD symptoms for veterans
6. Increased risks for youth
7. Increased risks for brain development damage

Increased Risk of Addiction

Increasing the potency of any drug increases the risk for addiction. A study in the UK in 2015 found that frequent use of Skunk (THC content around 15%) predicted a greater severity of dependence, this effect becoming stronger as age decreased. Whereby in contrast, the use of low potency cannabis (5%) was not associated with dependence.¹⁴ A 16-year observational study in the Netherlands found a positive time dependent association with increased THC potency and increased first-time admissions to drug treatment for cannabis use disorder.¹⁵

After observing the negative impacts from rising THC potencies, a team of health experts in the Netherlands concluded that THC potencies above 15% should be considered a hard drug like cocaine.¹⁶

Data obtained from the Wave 2 NESARC survey 2004-2005, when THC potency was less than 10 %, indicated that 8.9% of those who experiment with cannabis will become addicted.¹⁷ Then in the Wave 3 survey 2012-2013 this went up to 30% will become addicted.¹⁸ People who begin using cannabis before the age of 18 are 4-7 times more likely to develop a cannabis use disorder than adults.

It used to be thought that marijuana was not addicting and was referred to as a hallucinogen because hallucinogens do not have a withdrawal syndrome associated with their use.¹⁹ We now see a definite withdrawal syndrome from the higher potency cannabis, and it is a criterion for the diagnosis of cannabis use disorder.²⁰ Cannabis withdrawal syndrome is recognized by the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition, and requires the presence of at least 3 of the following symptoms developing within 7 days of reduced cannabis use: (1) irritability, anger ,or aggression; (2) nervousness or anxiety; (3) sleep disturbance; (4) appetite or weight disturbance; (5) restlessness; (6) depressed mood; and (7) somatic symptoms, such as headaches, sweating, nausea, vomiting, or abdominal pain.²¹

Increased Risk of Psychosis

There is increasingly strong evidence that higher potency cannabis use contributes to increased risk of psychosis. Numerous studies have demonstrated that using cannabis prior to the age of 15-18 significantly increases the risk of developing psychotic symptoms.²² A landmark study out of the UK analyzed 780 adults, ages 18-65, 410 with their first psychotic episode versus 370 matched healthy controls. It was found that the use of high potency THC >15% resulted in a three times increased risk of psychosis, and if the use was daily there was a five times increased risk. Those using < 5% THC did not exhibit psychotic symptoms.²³

This study was replicated in multiple sites in Europe and one site in Brazil and found the same outcomes, except this was for cannabis with 10% or more THC.²⁴ Using 10% or more THC resulted in a three times increased risk for psychotic symptoms and using daily resulted in a five times increased risk. In a recent systematic review and meta-analysis of 15 studies of psychiatric symptoms caused by cannabis constituents, the authors found that acute administration of THC induces significant increases in positive, negative, and other symptoms associated with schizophrenia and other mental disorders with large effect sizes in adults with no history of psychotic or other major psychiatric disorders.²⁵

Increased Risk of Violent Behavior

There is some evidence to suggest an association between persistent cannabis use and risk of violent behavior in individuals with serious psychiatric disorders. In one study 1,136 recently discharged psychiatric patients were followed at 4 10-week time intervals and evaluated for marijuana, alcohol and cocaine use as well as episodes of violence during the period 1992-1995. Persistent cannabis use was associated with an increased risk of subsequent violence, significantly more so than with alcohol or cocaine.²⁶

 In another study, 265 patients with early psychosis were followed prospectively for 36 months and dichotomized based on presence or absence of violent behavior. Cannabis use disorder (CUD) was the strongest risk factor of violent behavior with 61% of those with CUD versus 23% with no CUD exhibiting violent behavior.²⁷ The age of onset of cannabis use was 15 in violent patients versus 17 in non-violent patients. The use of cannabis was linked to impulsivity and lack of insight. Further research is needed to investigate this association.

A 2021 study of 3028 Iraq/Afghanistan-era veterans found that current Cannabis Use Disorder (CUD) was significantly positively associated with difficulty managing anger (OR = 2.93, p < .05), aggressive impulses/urges (OR = 2.74, p < .05), and problems controlling violence in past 30 days (OR = 2.71, p < .05), compared to those without CUD, even accounting for demographic variables, comorbid symptoms of depression and PTSD, and co-morbid alcohol and substance use disorders.²⁸

Increased Risk of Suicide

There is also increasing evidence that cannabis use is associated with violence towards oneself in the form of suicide. Multiple studies have documented a relationship between cannabis use and suicidality. A large longitudinal study in Australia and New Zealand of over 2000 adolescents and maximum frequency of marijuana use found almost a seven-fold increase in suicide attempts in daily marijuana users compared with non-users.²⁹ A 2017 cross-sectional multi-site VA study of 3233 Veterans found that cannabis use disorder was significantly associated with both current suicidal ideation (p<.0001) and lifetime history of suicide attempts (p<.0001) compared to Veterans with no lifetime history of cannabis use disorder.³⁰ The significance difference continued even after adjusting for sex, PTSD, depression, alcohol use disorder, non-cannabis drug use disorder, history of childhood sexual abuse and combat exposure.

Suicide is the number one cause of death in Colorado for individuals between the ages of 10 and 24 and cannabis is by far the most frequently encountered drug on toxicology screens of suicides among adolescents ages 10-19 and has been increasing over the last eight years according to the Colorado Department of Public Health and Environment.³¹ A large systematic review and meta-analysis of 11 studies of 23,327 adolescents found that cannabis use in adolescence significantly increased the risk of depression, anxiety and suicidality in young adulthood with an odds ratio of 3.5 for suicide attempts.³²

Increased PTSD Symptoms

Many people with post-traumatic stress disorder (PTSD) use cannabis to alleviate their symptoms and Colorado has approved PTSD as a condition for medical marijuana. However, this does not cure PTSD any more than alcohol or benzodiazepines cure PTSD. These substances can “numb” the person, so the symptoms are not bothersome but require the person to continue daily use to alleviate the symptoms, putting them at risk for addiction. There is strong evidence that persistent use of cannabis can make the PTSD symptoms worse and increase the risk of violence and suicidal ideation.^33,34

An observational study of 2276 veterans treated in PTSD treatment programs of the Veterans Administration around the country found that 4 months after participating in a month-long inpatient treatment program for PTSD, those who never used marijuana had significantly lower symptom severity, those who stopped using marijuana had the lowest level of PTSD symptoms 4 months after treatment and those who started to use marijuana had the highest levels of violent behavior and PTSD symptoms 4 months after treatment.³⁵

Recently the 2019–2020 National Health and Resilience in Veterans Study (NHRVS) followed 4,069 U.S. military veterans and found that frequent cannabis use worsens PTSD symptoms in military Veterans.³⁶ Compared with veterans who did not use cannabis or used it infrequently, those who used cannabis frequently were roughly twice as likely to screen positive for co-occurring Major Depressive Disorder, Generalized Anxiety Disorder, and Suicidal Ideation; showed small-to-moderate decrements in cognitive functioning; and were 2–6 times more likely to endorse using avoidance strategies as a primary means of managing their PTSD symptoms.

Increased Risks for Youth

Although national survey data indicate that use of marijuana by youth has remained stable, there has been a significant increase in dabbing and use of edibles as the usual method of marijuana use among high school students who reported past 30-day marijuana use in Colorado between 2015 and 2017.^37,38 These products are higher in THC potency and can result in more behavioral health consequences.A recent study from the UK of 1087 participants age 24, who started using cannabis between the ages of 14 and 16, found that those using the higher THC products (>10% THC) reported significant increased frequency of cannabis use, cannabis problems and increased likelihood of anxiety disorder compared to those using the products with <10% THC.³⁹  There has been a significant 10-year increase in adolescent marijuana-associated emergency department and urgent care visits in Colorado with a significant increase in behavioral health evaluations, most notably in the years following commercialization of medical (2009) and recreational marijuana (2014).⁴⁰

The use of electronic cigarettes (e-cigarettes) and vape devices by youth has rapidly increased, driven in large part by marketing and advertising by e-cigarette companies.⁴¹ In 2017 Colorado was leading the nation in use of nicotine-containing vapor products or vaping among young people under the age of 18 and this use was associated with a number of other risk behaviors including significantly more reports of marijuana use in the past 30 days.⁴² Among adolescents reporting use of electronic vapor products, 50.1% reported using marijuana in the past 30 days versus7.6% of those not using vape products.

Increased Risks of Brain Development Damage

One positive benefit of research on cannabis has been an increasing understanding of the endocannabinoid system in the brain. It was named as such because it was discovered that THC fit into a receptor in the brain in the 1960s, well before there was any understanding of why we might have such a receptor in the brain.⁴³ The same lab that discovered this, discovered why we have these receptors. In the 1990s they discovered the brain makes a substance, they named anandamides (which is a Sanskrit word for extreme joy or bliss) which fit into these cannabis receptors (CB1) in the brain.

Experimental evidence shows that the cannabinoid system activity is neuroprotective, regulating critical homeostatic processes in the brain.⁴⁴ The brain produces anandamides when needed; they are used locally and destroyed when no longer needed. CB1 receptors regulate the balance between excitatory and inhibitory neuronal activity. CB1 receptors play a particularly important role during adolescent brain development. THC fits into the CB1 receptors blocking anandamides and is slow to disappear. Adolescent/young adult exposure to cannabis can disrupt excitatory glutamate functioning in the brain. Glutamate plays an important role in normal brain development by facilitating synaptic pruning in the prefrontal motor cortex during adolescence and young adulthood. This process is not complete until the mid-20s when the brain is considered fully developed. ⁴⁹ As such the use of marijuana during development can cause long-term or possibly permanent adverse changes in the brain.⁴⁵

Recommendations for Limits on High-Potency THC

Given that research supporting the use of cannabis for medical conditions is limited to less than 10 % THC and use of products greater than 10 % THC can contribute to a myriad of problems, a strong recommendation is to:

1 > Limit potency of THC to under 10% in medical cannabis and eliminate the concentrates such as wax, shatter, oil for vaping, from medical cannabis since there is no research on these products for any medical condition.

2 > Eliminate edibles or significantly reduce the THC in edibles and prohibit any packaging that make edibles appear like current popular food items such as candies, cookies, etc.

References

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By Libby Stuyt, MD