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Risks of increasingly potent Cannabis: The joint effects of potency and frequency As THC levels rise, the risk of psychosis, cognitive deficits, and structural brain changes increases Joseph M. Pierre, MD n the United States, the average potency of Cannabis has increased Health Sciences Clinical Professor significantly over the past few decades in response to consumer Department of Psychiatry and Biobehavioral Sciences demand and policies in some states that have legalized marijuana I 1 David Geffen School of Medicine at UCLA for medicinal and recreational purposes. Whereas the delta-9-tetra- Los Angeles, California hydrocannabinol (THC) content of “street” marijuana was <1% in Disclosure the 1970s and 4% in the 1990s, by 2012, analyses of Cannabis samples The author reports no financial relationship with any company whose products are mentioned in this article or seized by law enforcement agencies documented a rise in average with manufacturers of competing products. THC potency to >12%.1-3 Although this increase in potency has been overstated in the media because studies did not control for the effects of changes in sampling methods on freshness, it is estimated that Cannabis potency increased 7-fold from 1970 to 2010.3 Also, Cannabis preparations such as hashish and hash oil extracts containing THC well above average—from 35% to 90% THC—are now more widely available. In states where marijuana has been legalized, high-potency Cannabis (HPC) in the form of “edi- bles” (eg, marijuana added to baked goods, candy, or drinks) and hash oil extracts (Table 1, page 16)4-13 can be readily obtained from dispensaries or even at local farmers’ markets. The potency of Cannabis, typically defined as the percentage of THC, its chief psychoactive component, varies depending on the genetic strain of the plant, cultivation techniques, and methods of process- ing and storage. For example, relative to “average marijuana,” hemp (Cannabis bred for industrial purposes) has very little THC, while sin- semilla (flowering buds from unpollinated female plants), hashish (Cannabis resin), and extracted hash oil contain increasing amounts of THC (Table 2, page 18).1,2 As THC levels in Cannabis have risen over time, cannabidiol (CBD) levels have dropped to <0.2%.2 Although THC appears to be largely Current Psychiatry TIM VERNON/SCIENCE SOURCE Vol. 16, No. 2 15 Table 1 Ultra-high potency Cannabis facts: Edibles and hashish oil extracts Marijuana ‘edibles’ • Marijuana “edibles” are food products (eg, baked goods, candy, drinks) that contain Cannabis • Edibles can contain significantly more THC compared with average smoked marijuana, although advertised potencies have been found to be inaccurate5 • Slow gastrointestinal absorption can result in a longer time to achieve a “high,” with accumulation High-potency of more Cannabis than was intended,6 difficulty predicting dosing effects,7 and potentially serious Cannabis adverse events including death8 • Edibles often are attractively packaged to resemble popular brand-name products, with particular appeal to minors9 Hash oil extracts • Ultra-high potency hash oil extracts are also known as “wax,” “dabs,” “crumble,” “budder,” or “shatter”10 • Hashish oil extracts may contain as much as 80% to 90% THC11 • Compared with conventional marijuana, hashish oil extracts may be associated with a greater risk of 11 4,12 13 Clinical Point tolerance and withdrawal, psychosis, and burns associated with preparation THC: delta-9-tetrahydrocannabinol The rise in the THC:CBD ratio raises the possibility that Cannabis use today responsible for the psychiatric morbidity This discrepancy could be explained might carry a greater associated with Cannabis, CBD may have if Cannabis users cut back past a specific neuroprotective and antipsychotic proper- threshold of increasing potency. However, risk of psychiatric ties.14,15 The sharp spike in the THC:CBD 2 studies have called into question how sequelae ratio in recent years therefore raises the pos- effective such titration efforts might be in sibility that Cannabis use today might carry practice. In one study, Cannabis users who a much greater risk of psychiatric sequelae preferred more potent Cannabis inhaled than it did in previous generations. lower volumes of smoke, but did not fully This article reviews the evidence for an compensate for the increased potency, such increased risk of psychiatric morbidity with that use of HPC still resulted in greater THC increasing Cannabis potency. exposure.18 Another study found that HPC users rolled less marijuana into their joints but not enough to mitigate the impact of Cannabis use disorder greater potency.19 Therefore, it appears that Recent data indicate that the prevalence HPC users typically expose themselves to of Cannabis use disorders (eg, abuse and greater amounts of THC, which could place dependence) in the United States is approxi- them at higher risk of addiction. mately 3% among the general population Although a causal association between and >30% among Cannabis users.16 The increasing Cannabis potency and the rate availability of increasingly potent forms of of substance use disorders among users Cannabis has been cited as a possible expla- remains unclear based on epidemiologic nation for this rise, despite no change in the studies from the United States, a recent prevalence of overall marijuana use between study from the United Kingdom examined 1991 to 1992 and 2001 to 2002.17 However, the impact of Cannabis potency on depen- Discuss this article at while the prevalence of marijuana use disor- dence.20 This cross-sectional survey found www.facebook.com/ ders has continued to rise—nearly doubling that, although HPC was preferred by users CurrentPsychiatry from 2001 to 2002 to 2012 to 2013—this latest and was rated as offering the “best high,” its increase occurred with a significant increase use was associated with increasing sever- in overall marijuana use, such that the ity of dependence, especially among young actual rate of Cannabis use disorders among people. The limited available evidence sup- users seems to have plateaued, despite ports a greater risk of Cannabis use disorders Current Psychiatry 16 February 2017 the continued rise in marijuana potency.16 with increasing potency. Psychosis first-episode psychosis, with daily HPC Based on longitudinal studies published users developing first-episode psychosis over the past 30 years, it is clear that using an average of 6 years earlier than non- Cannabis at a young age (age <15 to 18) Cannabis users.27 Finally, a prospective increases the risk of developing a psy- study following patients with first- chotic disorder.21 This association appears episode psychosis over 2 years found that to be dose-dependent, with studies con- the greatest risk of relapse—defined by sistently demonstrating that psychosis hospital admission caused by exacerba- risk increases with greater frequency of tion of psychotic symptoms—was found Cannabis use.22 The accumulated evidence among self-reported daily users of HPC, to date is strong enough to view the psy- while the lowest risk was among those chotic potential of Cannabis as a significant who stopped using Cannabis after their public health concern.21 initial psychotic episode.28 If risk of psychosis is proportional to the The findings from these 4 studies sug- amount of Cannabis used as measured by gest that the increased risk of psychosis frequency, it follows that this risk might with Cannabis is proportional to overall be affected similarly by Cannabis potency. exposure, determined by both frequency Clinical Point In another paper, I discussed the potential of use and Cannabis potency. The increased for greater risk of psychosis in the context of medical marijuana and synthetic can- risk of psychosis nabinoids.23 My colleagues and I also have Cognition with Cannabis is published case reports describing emerg- There is little doubt that using Cannabis proportional to overall ing psychosis among regular Cannabis can impair cognition acutely, “after all, this exposure, determined users after escalating to higher potency is the basic reason for its recreational use,” by both frequency medical marijuana24 and a hyperconcen- as one author wrote.29 As with psychosis, trated form of hash oil known as Cannabis the available evidence indicates that the and potency “wax” or “dabs” that contains as much as degree of cognitive impairment is related 90% THC.4 Preliminary anecdotal evidence to the frequency and duration of Cannabis supports the plausibility of HPC being use as well as age of onset of use.30,31 more psychotoxic than less potent forms. Few studies have assessed cognitive Several studies from a research group in functioning in relation to Cannabis potency the United Kingdom, where sinsemilla has with most only examining the effects of increasingly dominated the drug market, relatively low-potency Cannabis with incon- likewise have reported that the use of HPC sistent results. For example, 2 studies com- is associated with a greater risk of psycho- pared cognitive performance in individuals sis. The first of these studies, published in smoking Cannabis with 1.8% and 3.9% THC. 2009, found that adults hospitalized for One study found that using higher potency first-episode psychosis were more likely Cannabis resulted in prolonged time needed to have used HPC than healthy controls.25 to complete certain cognitive tasks,32 Among Cannabis users, HPC use was asso- whereas the other found greater impair- ciated with a 7-fold increased risk of psy- ment in performance on a decision-making chosis, with daily HPC use associated with task at both potencies compared with non- a 12-fold increased risk. users but no differences between the 2 dos- Based on a larger dataset, a second ages.33 Detecting significant differences may study reported that high-potency, but not be difficult within the narrow range of low low-potency, Cannabis increased the risk Cannabis potency studied where any find- of first-episode psychosis with increas- ings have limited applicability in the con- ing frequency of use.26 Daily users of text of today’s Cannabis with much higher HPC had a 5-fold higher risk of psychosis THC content.

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