COMMENTARY

Medical Marijuana: The State of the Science

Michael E. Schatman, PhD

Disclosures

February 06, 2015

In This Article

Cannabis Use and Mental Health

Relative to the literature on the physical health effects of cannabis use, the available literature on its mental health effects is quite abundant. Despite years of the widely embraced opinion to the contrary, we now know that cannabis is addictive. Symptoms specified in the fifth edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-5) for cannabis withdrawal include irritability, nervousness, sleep difficulty, decreased appetite, restlessness, depressed mood, and physical symptoms and discomfort.[40] The inclusion of all of these symptoms is supported by a broad base of evidence.[41,42,43,44]

Depersonalization among cannabis users has been recognized for many years[45]; this may be related to residual neurotoxicity associated with cannabis and the extended elimination half-life of cannabis metabolites.[46]

The relationship between cannabis use and various psychopathologies and related psychiatric hospitalizations is gaining more attention with increased medical use.[47] As early as 1944, Allentuck[48] reported on the development of anxiety and dysphoria among study participants who received marijuana experimentally. Subsequently, hundreds of articles addressing negative emotional responses to marijuana have appeared in the literature.

A recent review[49] concluded that the adverse psychological effects of marijuana are caused by THC and mitigated by CBD. Acute anxiety in response to THC is becoming more common as THC concentrations increase; lower concentrations tend to be anxiolytic, whereas higher concentrations tend to produce anxiety.[50] However, although frequent marijuana smokers have a high prevalence of anxiety disorders and likewise, individuals with anxiety disorders have relatively high rates of marijuana use, we do not have sufficient evidence to determine whether marijuana use actually causes chronic anxiety disorders.[51]

Data suggest that long-term use of marijuana increases the risk for depression,[52] leads to more pronounced suicidal ideation,[53] and heightens risk for suicide attempts.[54] Of particular concern has been the susceptibility of the developing brain to depression and anxiety resulting from marijuana use. In a prospective cohort study,[55] frequent marijuana use by teens predicted depression and anxiety later in life, and a more recent study[56] determined that use of marijuana among adolescents was associated with adult-onset anxiety. However, the relationship between marijuana use and depression may by confounded by "common genetic influences."[57]

The association between bipolar disorder and marijuana use is unclear; however, a recent systematic review[58] found an association between cannabis use and earlier onset of initial mania and more frequent manic or depressive episodes. Despite this apparent association, the causal relationship between cannabis and onset of mania remains unclear.

A growing body of literature supports the relationship between marijuana use and psychotic disorders, with acute and transient effects, acute and persistent effects, and delayed and persistent effects "that bear a striking resemblance to symptoms of schizophrenia" as seen in both observational and experimental studies.[59] Early and heavy cannabis exposure has been associated with psychosis later in life in numerous studies.[60,61,62,63] However, a recent review[64] indicated that exposure to cannabis can also result in acute psychotomimetic symptoms that may not persist beyond the period of intoxication.

Several risk factors have been implicated in augmenting the association between cannabis and psychosis; these include early age of exposure,[65] history of childhood abuse,[66] and family history of schizophrenia.[67] Many genetic factors are believed to confer vulnerability to psychosis in individuals exposed to cannabis,[68,69,70] representing a gene/environment interaction. In their recent review, Radhakrishnan and colleagues[59] concluded that "the association between cannabis and psychosis fulfills many, but not all of the standard criteria for causality." The evidence for causality, however, is rapidly increasing.

Cannabis and Cognition

Published data support that heavy, long-term use of marijuana results in impairment in several areas of cognitive functioning. An evidence-based review of the literature[71] found that heavy use of cannabis acutely impairs attention and concentration, inhibition and impulsivity, and working memory; findings for decision-making and risk-taking were mixed. However, in a study that used neuroimaging studies to evaluate the effect of marijuana on memory functioning, this relationship was difficult to interpret, given major differences in characteristics of the study populations involved.[72]

The misperception that marijuana causes only transient cognitive impairments was rebuked by a recent prospective cohort study of over 1000 participants followed from birth until 38 years of age,[73] which found that neuropsychological functioning was not fully restored among adolescent marijuana users after cessation. Although the extent to which long-term cannabis use results in permanent cognitive impairment remains controversial, the growing evidence of structural changes to the integrity of the brain due to chronic use among adults may be a significant concern for patients who use medical marijuana on a regular basis.[74]

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