KINDLAND ARTICLE Editorial Director. Author of 'Prisoner of X' and 'Punk Elegies.'
People are forever wandering onto KINDLAND territory and wondering out loud: What makes you people so goddamn smart?
Well, scientific findings recently published in Frontiers in Pharmacologymay have cleared up that mystery once and for all. Preliminary investigations by medical researchers from McLean Hospital, Harvard Medical School, and Tufts University indicate that pot use improves cognitive performance.
Cognitive performance, no need to tell you, is “our ability to utilize the knowledge acquired by mental processes in our brains.” In other words, perform tasks that require thinking, as in to be so goddamn smart.
The behavioral scientists behind the work summarized in “Splendor in the Grass? A Pilot Study Assessing the Impact of Medical Marijuana on Executive Function” tracked 24 certified medical-marijuana patients over a three-month dosing period. The patients were repeatedly measured for cognitive proficiency through challenges to the intelligence that included the Stroop Color Word Test and Trail Making Test.
Staci Gruber, PhD, director of the Marijuana Investigations for Neuroscientific Discovery (MIND) program at McLean Hospital—Harvard Medical School’s largest psychiatric affiliate—is the lead “Splendor in the Grass?” researcher. Her initial report is twofold positive. For one thing, weed treatment led to patients breezing through an array of brainteasers with enhanced speed and accuracy. (continue reading)
Splendor in the Grass? A Pilot Study Assessing the Impact of Medical Marijuana on Executive Function
Staci A. Gruber1,2*, Kelly A. Sagar1,2, Mary K. Dahlgren1,3, Megan T. Racine1, Rosemary T. Smith1 and Scott E. Lukas2,4
- 1Cognitive and Clinical Neuroimaging Core, McLean Hospital Imaging Center, Belmont, MA, USA
- 2Department of Psychiatry, Harvard Medical School, Boston, MA, USA
- 3Department of Psychology, Tufts University, Medford, MA, USA
- 4Behavioral Psychopharmacology Research Laboratory, McLean Hospital Imaging Center, McLean Hospital, Belmont, MA, USA
Currently, 25 states and Washington DC have enacted full medical marijuana (MMJ) programs while 18 states allow limited access to MMJ products. Limited access states permit low (or zero) tetrahydrocannabinol (THC) and high cannabidiol (CBD) products to treat specified conditions such as uncontrolled epilepsy. Although MMJ products are derived from the same plant species as recreational MJ, they are often selected for their unique cannabinoid constituents and ratios, not typically sought by recreational users, which may impact neurocognitive outcomes. To date, few studies have investigated the potential impact of MMJ use on cognitive performance, despite a well-documented association between recreational marijuana (MJ) use and executive dysfunction. The current study assessed the impact of 3 months of MMJ treatment on executive function, exploring whether MMJ patients would experience improvement in cognitive functioning, perhaps related to primary symptom alleviation. As part of a larger longitudinal study, 24 patients certified for MMJ use completed baseline executive function assessments and 11 of these so far have returned for their first follow-up visit 3 months after initiating treatment. Results suggest that in general, MMJ patients experienced some improvement on measures of executive functioning, including the Stroop Color Word Test and Trail Making Test, mostly reflected as increased speed in completing tasks without a loss of accuracy. On self-report questionnaires, patients also indicated moderate improvements in clinical state, including reduced sleep disturbance, decreased symptoms of depression, attenuated impulsivity, and positive changes in some aspects of quality of life. Additionally, patients reported a notable decrease in their use of conventional pharmaceutical agents from baseline, with opiate use declining more than 42%. While intriguing, these findings are preliminary and warrant further investigation at additional time points and in larger sample sizes. Given the likelihood of increased MMJ use across the country, it is imperative to determine the potential impact of short- and long-term treatment on cognitive performance as well as the efficacy of MMJ treatment itself.
Over the last several decades, although marijuana (MJ) users in the US have historically sought out MJ for recreational purposes, a growing number are exploring MJ for medical purposes. In fact, it is estimated that over 1.2 million medical MJ (MMJ) consumers are currently registered in the US (Procon.org1). According to Procon.org, although the majority of states have mandatory MMJ registration (CO, MA) other states have voluntary registration (e.g., CA, ME) or do not require registration (WA). While the number of current US MMJ consumers is only an estimate, it is likely that the number of certified patients will continue to grow as the public becomes increasingly aware of and open to the potential therapeutic effects of MMJ. Legal marijuana is considered the fastest growing market in the United States, with a current estimated value of $6.7 billion, which could reach 21.8 billion by 2020 (ArcView Market Research, 2016). In 1996, California became the first state to fully legalize MMJ and since then, another 24 states, and the District of Columbia have followed suit with full legalization for medical purposes, while an additional 18 states have limited MMJ laws, allowing only the use of products containing a specific non-psychoactive cannabinoid (cannabidiol [CBD]). Four states and the District of Columbia have also approved recreational MJ use, with several additional states pending legislation. Recent national surveys (Center for Behavioral Health Statistics and Quality, 2015; Johnston et al., 2015) report that MJ is retaining its status as the most widely used illicit drug for recreational purposes in the world; nearly 22.2 million Americans report use within the past month (Center for Behavioral Health Statistics and Quality, 2015). Further, while more than a million Americans are registered MMJ patients, this estimate does not include the unknown number of consumers currently taking hemp-derived products, marketed as high CBD-containing compounds (tinctures, oils, topicals), which are widely available from a number of vendors who do not require MMJ certification. Despite the rapid changes in policy, many legislators, consumers, physicians, and the general public remain misinformed about MJ. Although used for centuries as medicine by varied cultures across the world, in the US, MMJ became part of mainstream medicine in 1850, when it was added to the US Pharmacopeia. Physicians prescribed the use of MJ broadly for a range of indications including (but not limited to) pain, emesis, migraine, insomnia, epilepsy, and opium withdrawal (Birch, 1889; Potter, 1917; Grinspoon and Bakalar, 1997; Booth, 2003) and it remained widely available until 1937, when the marijuana tax law criminalized use of the substance. As anti-MJ sentiments grew across the country, it was removed from the pharmacopeia in 1942 and in 1970, the passage of the Controlled Substances Act (CSA) declared MJ a Schedule I substance and the cultivation, possession, and distribution of MJ became prohibited. According to the Drug Enforcement Administration (DEA), Schedule I drugs are those “with no currently accepted medical use, no demonstrated safety profile and a high potential for abuse…[they] are the most dangerous drugs of all the drug schedules with potentially severe psychological or physical dependence” (dea.gov2; Comprehensive Drug Abuse Prevention and Control Act of 19703). This classification deems MJ more dangerous than other substances including cocaine, methamphetamine, and opiate-based drugs, which ironically are responsible for approximately 30,000 deaths per year (Centers for Disease Control and Prevention, 2015). In fact, opioid overdoses are now considered a national epidemic; the rate of opioid overdose deaths, including those related to both prescription pain relievers and heroin, has nearly quadrupled since 1999 (Centers for Disease Control and Prevention, 2015). Given its Schedule I classification, research studies exploring both potential risks and benefits of MMJ have faced numerous obstacles, forcing policy to outpace science in recent years. As the national climate warms toward MJ, research is slowly pushing forward. However, much is left to be explored before the gap between science and policy can begin to close.
A growing body of evidence suggests that recreational MJ use adversely impacts the brain, particularly during critical periods of neurodevelopment, including adolescence (For review: Crean et al., 2011; Jacobus and Tapert, 2014; Lisdahl et al., 2014). Numerous studies have shown that MJ users, particularly those who initiate use during adolescence, exhibit deficits across multiple cognitive domains. For example, MJ users who initiate use during adolescence exhibit deficits in attention (Ehrenreich et al., 1999; Cousijn et al., 2013; Becker et al., 2014) and processing speed (Fried et al., 2005; Medina et al., 2007; Lisdahl and Price, 2012; Jacobus et al., 2015). Furthermore, lower scores on measures of IQ (Pope et al., 2003; Meier et al., 2012; Crane et al., 2015) have been observed among adolescent MJ users, although recent work has questioned this finding (Jackson et al., 2016; Mokrysz et al., 2016), and a number of studies have reported poorer verbal memory among adolescent and adult MJ smokers (Tait et al., 2011; Auer et al., 2016; Shuster et al., 2016). Data also suggest that adolescent MJ use is strongly associated with poorer executive functioning (Fontes et al., 2011; Solowij et al., 2012; Crane et al., 2013; Dougherty et al., 2013; Tamm et al., 2013; Becker et al., 2014; Hanson et al., 2014; Winward et al., 2014; Jacobus et al., 2015; Sagar et al., 2015) even when deficits in other domains are not observed (Gruber et al., 2012a).
In contrast, although research is in its infancy, given what is currently known about MJ, it is possible that MMJ use may not lead to the same neurocognitive consequences that have been observed in recreational users. Although recreational and medical MJ are derived from the same plant species, there are inherent differences that exist between the two. As recreational users most frequently seek a mood altering, often “euphoric” or “mellow” state, they primarily utilize products with considerable amounts of THC, the main psychoactive ingredient in MJ (Wachtel et al., 2002; Zeiger et al., 2010). Over the last two decades the potency of recreational marijuana has significantly increased from approximately 4 to 12% between 1995 and 2014 in response to consumer demand (ElSohly et al., 2016). In contrast, MMJ users primarily initiate MMJ use as a means of symptom alleviation (Nunberg et al., 2013), and as such are likely to seek products for their therapeutic potential rather than to experience the psychoactive effects. They may therefore use products differently and purchase products with a markedly different chemical composition from more common recreational products. These MMJ products are often (but not always) high in other cannabinoids, such as cannabidiol (CBD) which has been touted for its therapeutic potential, and which is not psychoactive. CBD has become best known in recent years for its potential to treat those with intractable seizure disorders, specifically children with Dravet Syndrome or Lennox Gastaux Syndrome, and preliminary data from both anecdotal reports and recent clinical trials are promising. In a recent open-label trial in patients aged 1–30 with severe, intractable, childhood-onset, treatment-resistant epilepsy, Devinsky et al. (2016) reported that the median monthly frequency of motor seizures decreased from 30 per month at baseline to 15.8 per month during the treatment period in patients treated with Epidolex, a 98% purified CBD compound created by GW Pharma. CBD has also demonstrated promise in treating other conditions including chronic pain, multiple sclerosis (Giacoppo et al., 2015), and Huntington's disease (Consroe et al., 1991) as well as psychiatric and behavioral health conditions including anxiety (for review: Blessing et al., 2015) and psychosis (Zuardi et al., 2009; Leweke et al., 2012). Interestingly, some work suggests that CBD may have a pharmacological profile similar to that of antipsychotic medications (Zuardi et al., 2012). In addition to CBD, a host of other cannabinoids, many of which are non-psychoactive, are also often present in MMJ products, and becoming increasingly popular. Other phytocannabinoids, including cannabigerol (CBG), cannabinol (CBN), cannabichromene (CBC), tetrahydrocannabinolic acid (THCA), and tetrahydrocannabidivarin (THCV), have shown therapeutic potential and may also reduce some of the undesirable effects associated with THC. For example, cannabichromene (CBC), another abundant cannabinoid, has anti-inflammatory effects (Izzo et al., 2012) and has recently been shown to increase the viability of adult neural stem progenitor cells (NSPCs), essential for brain plasticity and suggestive of neurogenesis (Shinjyo and Di Marzo, 2013). In addition, cannabigerol (CBG) inhibits GABA uptake, has anti-inflammatory properties, and has also been touted as being neurogenic (Borelli et al., 2013; Valdeolivas et al., 2015), while tetrahydrocannabidivarin (THCV) has been shown to inhibit some of the negative cognitive and physiologic effects of THC and may be neuroprotective (Englund et al., 2016).
Despite the majority of states with MMJ laws and more than a million registered patients, no studies to date have utilized a pre- vs. post-design model to examine the specific impact of MMJ on cognitive performance as a primary outcome variable. As noted above, cognitive deficits are demonstrated in chronic, heavy, recreational MJ users who begin MJ use during adolescence (for review: Crean et al., 2011; Jacobus and Tapert, 2014; Lisdahl et al., 2014), and while some clinical trials of MMJ (particularly CBD) have been initiated in children for treatment-resistant epilepsy (Devinsky et al., 2016), the majority of those utilizing MMJ products are adults, and beyond the most critical period of neurodevelopmental vulnerability. In addition, it is likely that if physical or psychological symptoms are addressed by MMJ use, cognitive function may improve. For example, studies have reported that anxiety often interferes with both attention and executive function (e.g., Vytal et al., 2013); if MMJ products act as an anxiolytic for at least some patients as reported, this may result in better concentration and enhanced cognitive performance. Chronic pain has also been noted to impair cognitive performance, notably tasks requiring attentional and executive function (for review see Moriarty et al., 2011). Accordingly, if patients experience a reduction in pain-related symptoms as a result of MMJ treatment, it is likely that cognitive performance will improve relative to a pre-treatment assessment.
In order to evaluate the impact of MMJ use on cognitive function and determine the efficacy of MMJ in a broad sample of MMJ patients, we designed a longitudinal study which assesses MMJ patients at baseline and after 3, 6, and 12 months of MMJ treatment. Importantly, baseline measurements were taken prior to the initiation of MMJ treatment in order to obtain an “MJ naïve” assessment. Given the differences between MMJ and recreational MJ use and the reported potential for symptom alleviation in MMJ users, we hypothesized that MMJ patients would demonstrate improved cognitive performance on tasks of executive functioning, as well as improved clinical state and quality of life following MMJ treatment. This study is currently ongoing, and in this paper, we report our preliminary cognitive findings in addition to information regarding general health and clinical state measures as well as medication use, after 3 months of MMJ treatment. (full report)