Health effects of cannabis: the recent National Academy review and beyond
The National Academy of Sciences, Engineering, and Medicine recently issued a report using weight-of-evidence categories in reviewing and evaluating the overall scientific literature that supports therapeutic and other health effects of cannabis or cannabinoids.3 The report concluded that there are several clinical problems for which there is conclusive or substantial evidence that cannabis or cannabinoids are effective—chronic pain, chemotherapy-induced nausea and vomiting, and patient-reported multiple sclerosis spasticity symptoms.
The report also concluded that there is moderate evidence that cannabis or cannabinoids are effective for improving short-term sleep outcomes in individuals with sleep disturbances associated with a variety of conditions. While none of those conditions is regarded as a psychiatric disorder, they all can be associated with other psychiatric symptoms (beyond sleep disturbance) and are all encountered by psychiatrists as comorbid conditions in clinical practice: obstructive sleep apnea, fibromyalgia, chronic pain, and multiple sclerosis. Sleep disturbances are also ubiquitous in the nosological schemes of psychiatry, notably in PTSD where nightmares are a factor.
At the community level, psychiatrists often advise against cannabis use, while some may recommend or approve it as an adjunctive therapeutic for patients with specific diagnostic entities and/or target symptoms. Patient reports that cannabis may relieve some of their symptoms are corroborated by a growing body of clinical literature that is as yet underdeveloped from a research perspective.1 For other patients, the expression of a psychotic disorder may have been preceded by long-term cannabis use and/or cannabis use may be seen as an ongoing factor that exacerbates symptoms of mental illness.
The National Academy report concluded that there is substantial evidence of a statistical association between cannabis use and the development of schizophrenia or other psychoses, and that the risk is highest among the most frequent users. The increased risk is a weak effect, and the causal implications of the association unclear. Although cannabis use may lead to exacerbation of psychosis in some patients, the possibility remains that patient use for symptom relief may account in part for the statistical association.
Schizophrenia, CBD, and THC
Molecular CBD has been shown to treat symptoms of schizophrenia under controlled clinical trial conditions, with results comparable to those of treatment with an approved antipsychotic medication, and with a favorable adverse-effect profile.4 Other studies support the view that CBD may have therapeutic potential as an antipsychotic and may counter or offset psychotomimetic effects of THC. Differences between THC and CBD notwithstanding, in a small case series, 6 patients with schizophrenia and a history of symptom relief with cannabis use were treated with the addition of low-dose prescription THC to regimens that included clozapine in some cases or multiple antipsychotics in 1 patient.5 Four of the 6 patients showed improvement with the addition of THC to their regimen, and in 3 of the 4 patients a specific antipsychotic effect was evident. As with the anxiogenic potential of THC, dosage may be important in the relationship between THC and psychosis.
Cannabis and cognition
The National Academy report also acknowledged that there is moderate evidence of a statistical association between cannabis use and better cognitive performance among individuals with psychotic disorders and a history of cannabis use. It has been speculated that this could represent a less cognitively vulnerable subgroup of patients who would not have developed psychosis in the absence of exposure to cannabis, but this is not known. More generally, there is moderate evidence of a statistical association between acute cannabis use and impairment in the cognitive domains of learning, memory, and attention. However, results have been mixed on the question of longer-term and residual cognitive impairment. A recent report indicates neuropsychological decline in persistent long-term users with cannabis use disorders, although an earlier meta-analysis found no residual impairment.6,7 Evidence of impaired academic achievement and educational outcomes was judged to be limited according to the National Academy report. Again, with cognitive functioning as with the risk of psychosis, dosage may be an important factor, since the findings of impairment relate primarily to heavy long-term use and even more specifically to those patients with cannabis use disorders.
Cannabis, cannabinoids, and dementia
Although the National Academy report did not find evidence of therapeutic effects of cannabis or cannabinoids for symptoms associated with dementia, several interesting findings in this area are worth mentioning. Basic scientific evidence suggests that cannabinoids may suppress neuronal excitotoxicity and neuroinflammation and be potentially beneficial in targeting plaque formation in Alzheimer disease.8 However, the only clinical applications of cannabinoids in patients with dementia have involved targeting behavioral disturbances including agitation, food refusal, and irritability in small open studies with reported success.
A recent single-photon emission computed tomography study of patients with cannabis use disorders found decreased cerebral blood flow in a number of regions including the hippocampus. The investigators speculated that individuals with cannabis use disorders may be at increased risk for Alzheimer disease based on previous findings relating that risk to decreased hippocampal blood flow.9 Further studies will be necessary to investigate the potential therapeutic applications of cannabinoids in dementia, and whether excessive long-term cannabis use is a potential risk factor.
Dr. Fichtner reports no conflicts of interest concerning the subject matter of this article. Dr. Moss reports that he owns 24 common stock shares of GW Pharmaceuticals currently valued at $2900 in his IRA. GW Pharmaceuticals is the maker of the drugs Sativex and Epideolex.
Dr. Fichtner and Dr. Moss are Clinical Professors of Psychiatry at the University of California, Riverside School of Medicine.
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