From the Editor
“It’s the only thing that works.”
So many of our patients swear by cannabis. It has become a popular choice for everything from anxiety to chronic pain. And though the literature is relatively young, now we know more about cannabis than before. This week, we focus on three new papers.
The first selection is a paper by Dr. Emmet Power (of the Royal College of Surgeons in Ireland) and his co-authors from Psychological Medicine. Does frequent and dependent cannabis use in youth affect IQ? Doing a systematic review and meta-analysis, they find seven papers. They conclude: “We found that young people who use cannabis frequently or dependently by age 18 have declined in IQ at follow up and this may be due to a decline in verbal IQ.”
In the second selection, we consider a new paper from Psychiatric Services. Dr. Corneliu N. Stanciu (of Dartmouth College) and his co-authors did a systematic review of cannabis for several disorders. “With only eight very small studies, insufficient evidence was found for efficacy of CBD and THC to manage affective disorders, anxiety disorders, or PTSD.”
Finally, in the third selection, we look at a paper from Annals of Internal Medicine. Drs. Arthur Robin Williams (of Columbia University) and Kevin P. Hill (of Harvard University) pose 15 questions about cannabis and answer them. The authors are practical and thoughtful. The clinical bottom line: “Millions more adults now meet criteria for cannabis use disorder in a given year, and all clinicians, not just mental health professionals, have vital roles in improving clinical management, from screening and diagnosis to overseeing treatment plans.”
Selection 1: “Intelligence quotient decline following frequent or dependent cannabis use in youth: a systematic review and meta-analysis of longitudinal studies”
Emmet Power, Sophie Sabherwal, Colm Healy, et al.
Psychological Medicine, 27 January 2021 Online First
Cannabis is the most frequently used illicit substance worldwide, with the prevalence of lifetime cannabis use highest in young people. Cannabis use in adolescence is consistently associated with poorer mental health outcomes including increased risk of mood disorders, self-harm and suicidality. Cannabis use is also associated with markedly poorer psychosocial outcomes across the lifespan in diverse indices such as educational attainment, employment, relationships, welfare dependency, risk of motor accidents, social mobility and income. There is strong evidence demonstrating an association between cannabis and psychotic disorders, particularly frequent use of high tetrahydrocannabinol potency cannabis…
Cannabis use during youth is of particular concern, as the developing brain may be particularly susceptible to harm during this period. A New Zealand cohort study has shown that persistent cannabis dependency from adolescence to midlife has previously been associated with a clinically significant eight-point decline in Intelligence Quotient (IQ)…
Previous meta-analyses show inconsistent and heterogeneous findings for both global and specific cognitive domains relating to cannabis use.
So begins a paper by Power et al.
Here’s what they did:
- They conducted a systematic review and meta-analysis.
- They searched databases including Embase, PubMed, and PsychInfo from inception to 24 January 2020. And they requested data from authors if summary data was not available from published work.
- “We included prospective cohort studies of non-treatment seeking youth from samples recruited from the community with a baseline measurement of IQ prior to participants initiating cannabis use. We specified that the onset of cannabis use should have occurred at or before age 26. We specified that participants should have both a baseline and follow-up measure of IQ.”
- Cannabis exposure was defined as “at minimum weekly use for 6 months and/or >25 reported lifetime uses and/ or diagnosis of cannabis dependency.”
Here’s what they found:
- “We identified 33 papers for full-text screening… We included seven studies that met our criteria. The seven cohorts included in this meta-analysis contain 808 cases and 5308 controls from four Western countries.”
- “We found a significant overall effect for the association between frequent or dependent cannabis use and IQ change [Cohen’s d = −0.132]. This corresponds to a 1.98-point decline in IQ (95% CI 0.99–2.97).”
- “We extracted verbal IQ change effect sizes from four available studies. The pooled effect size of verbal IQ decline was d = −0.196… This corresponds to a decline of 2.94 verbal IQ points…”
- “There was no evidence of relative baseline full-scale IQ differences between frequent/dependent cannabis users and non-users…”
- Study quality was moderate to high.
“This is the first longitudinal quantitative synthesis to our knowledge examining the association between frequent or dependent cannabis use during adolescence and IQ change over time. We found that young people who use cannabis frequently or dependently by age 18 have declined in IQ at follow up and this may be due to a decline in verbal IQ.”
A few thoughts:
- This is a good study.
- The seven studies varied greatly in the numbers of subjects. The Canadian study (Fried et al.), for instance, only had 38 people who were “exposed.” But the findings of IQ change were consistent across the different studies.
- The authors themselves cast doubt on the clinical significance. “The approximately 2-point decline in IQ in adolescent-onset frequent cannabis users is not to be clinically significant and alone is unlikely to completely explain a range of psychosocial problems linked to cannabis use in this cohort.”
- The authors draw on studies that tended to have a short follow up period. Would more problems have been captured with a longer time horizon? The New Zealand cohort study mentioned at the opening of the paper (and included in the analysis) did follow up with people into mid-life; they found an eight-point change in IQ. (!!)
The full paper can be found here:
Selection 2: “Evidence for Use of Cannabinoids in Mood Disorders, Anxiety Disorders, and PTSD: A Systematic Review”
Corneliu N. Stanciu, Mary F. Brunette, Nikhil Teja, Alan J. Budney
Psychiatric Services, 3 February 2021 Online First
Humans have utilized products from cannabis plant species for millennia – for example, ancient Chinese literature discussed the perceived medicinal values of cannabis several thousand years ago. Recreational use of cannabis species containing relatively high levels of delta-9-tetrahydrocannabinol (THC) became widespread in the western world in the 19th century and grew increasing popular in the United States later in the 20th century. In the 1970s, the U.S. Drug Enforcement Administration scheduled cannabis as a substance with high abuse potential and no known medicinal value, but illegal recreational use continued to be common. Since then, researchers have begun to explore whether cannabis has medicinal value, although this work has been slowed by strict regulations on studies that administer cannabis to humans.
As state efforts to legalize cannabis for medical and recreational purposes were increasingly successful over the past 10 years, public perceptions have shifted away from viewing cannabis as harmful. Almost half of the American public has endorsed the belief that cannabis may provide relief from anxiety and depression. Thus, in states where cannabis is legal for medical use, people approach their physicians to seek medical cannabis for symptoms of anxiety and depression, and over a third of people who use medical cannabis have reported using it to reduce anxiety. To date, 28 states list posttraumatic stress disorder (PTSD) as a potentially qualifiable condition for certification of cannabis purchase and use, one state lists anxiety, and one state lists refractory generalized anxiety disorder, but none specifically lists depressive disorders.
So begins a paper by Stanciu et al.
Here’s what they did:
- They searched various databases, including PubMed, for English-language papers published between January 1, 1970, and February 5, 2020.
- Keywords included “cannabidiol AND anxiety.”
- “All studies reporting prospective, randomized, and controlled trials involving humans with specified doses of whole-plant cannabis or of CBD, THC, or both compounds compared with placebo were considered.”
Here’s what they found:
- “Among the eight studies meeting our criteria, two included persons with DSM-I or DSM-II anxiety disorders, three included individuals with social anxiety disorder, one included persons with PTSD, and two included persons with mood disorders during a depression episode. Seven studies used a double-blind, randomized design with a placebo control, and one study used a single-blind Latin square design.”
- CBD and THC for Anxiety Disorders. “Two small studies reported mixed findings on the impact of synthetic THC on various anxiety conditions. Another two studies of single-dose CBD and one of daily-dosed CBD for 4 weeks among individuals with social anxiety disorders reported beneficial effects of CBD.”
- THC and CBD for PTSD. “One very small randomized, double-blind, and placebo-controlled crossover study investigated the effectiveness of nabilone for decreasing the frequency and intensity of trauma-related nightmares associated with PTSD…”
- THC and CBD for Affective Disorders. “Two controlled trials in the 1970s evaluated THC for the treatment of patients with unipolar and bipolar depressive disorders. Both trials failed to show significant antidepressant effects of THC and indicated that it has poor tolerability…”
“On the basis of existing studies that included control conditions, randomization, and prospective blinded assessments, we found that there is not enough research to adequately determine the efficacy of THC alone, CBD alone, defined CBD-THC combinations, or plant marijuana to treat individuals with anxiety disorders, affective disorders, or PTSD.”
- This is a good paper.
- That being said, perspective: the total number of studies and total participants were small.
- As the authors note: “In total, only 112 participants were studied across eight small trials, five of which included ≤13 participants. Furthermore, only two of these studies evaluated participants for a clinically relevant period (1 month), and none of the studies examined cannabinoid combinations or smoked whole plant.”
- Cannabis enthusiasts claim that the drug is helpful for a variety of psychiatric conditions. This study suggests that, at least currently, the literature doesn’t support such claims.
- We are in the early days of research in this area.
The full paper can be found here:
Selection 3: “Care of the Patient Using Cannabis”
Arthur Robin Williams and Kevin P. Hill
Annals of Internal Medicine, 3 November 2020
The past 2 decades have seen a revolution in legal access to cannabis, driven largely by activists and business interests. As a result, the population of cannabis users nationwide – especially daily users – has grown significantly. An estimated 4.5-7 million persons in the United States now meet criteria for cannabis use disorder annually. This article focuses on the effects of cannabis use, intoxication, and withdrawal while also reviewing the developmental pathways of cannabis use disorder as well as evidence-based pharmacologic and psychosocial treatments.
So opens a paper by Drs. Williams and Hill.
The authors ask and answer 15 questions. Here, we summarize four:
What is hyperemesis syndrome?
“Cannabinoid hyperemesis syndrome has become more widely recognized in the past few years given increased rates of heavy use of high-strength cannabis. Patients may report taking an excessive number of hot showers, which can provide temporary symptom relief. Acute presentations may or may not involve intoxication on presentation; often include intractable nausea and vomiting lasting days to months; and may be especially difficult to control among patients with comorbid or poorly controlled migraine, psychiatric disorders, or opioid use disorders… Short-term treatment often relies on a sedative–hypnotic, such as lorazepam, and antipsychotics with an antiemetic, such as promethazine or ondansetron for breakthrough nausea.”
Is cannabis use safe during pregnancy?
“Patients should not use cannabis during pregnancy or while breastfeeding. However, data show that rates of cannabis use among pregnant women have increased dramatically in recent years after expanded legalization.”
Should clinicians screen for cannabis use, and if so, how?
“Validated screening tools are recommended. The 2 most commonly used tools for adolescents are the Screening to Brief Intervention (S2BI) and the Brief Screener for Tobacco, Alcohol, and other Drugs (BSTAD), both of which are available on NIDAMED.”
Is cannabis useful for treating pain?
“For many years, there have been anecdotal reports of pain relief from regular cannabis use. Chronic pain is the most common qualifying condition for medical cannabis reported by patients nationwide. However, the evidence for cannabis and cannabinoids as treatment for pain is mixed. Beyond the indications for which cannabinoids are FDA-approved, multiple randomized controlled trials and systematic reviews support their use for chronic pain, including neuropathic pain. The National Academies of Sciences, Engineering, and Medicine Committee on the Health Effects of Marijuana concluded that there is ‘conclusive or substantial evidence’ that cannabis is effective for the treatment of chronic pain in adults, based on the expert committee’s assessment that the literature on chronic pain has many supportive findings from good-quality studies with no credible opposing findings. In addition, a meta-analysis of 28 studies found moderate-quality evidence supporting the use of cannabinoids in treatment of chronic pain.”
A few thoughts:
- This is a highly readable and practical paper. As a clinician, you should read it.
- The paper draws from the evidence available.
- I’ll repeat my comment made with the Stanciu et al. paper: We are in the early days of research in this area. With that in mind, our clinical understanding is going to change with time.
The full paper can be found here:
Reading of the Week. Every week I pick articles and papers from the world of Psychiatry.