COMMENTARY

Medical Marijuana: The State of the Science

Michael E. Schatman, PhD

Disclosures

February 06, 2015

In This Article

CBD: Some Semblance of Coherence?

CBD is finally becoming established in US medicine, not just in terms of developing an evidence basis but also in its increased legalization, availability, and clinical use. CBD is safer and more uniform in its composition than "medical marijuana," and it is associated with less variability in response to it, thereby giving it greater clinical value. In discussing variance in THC levels among strains, Smith[94] wrote, "Cannabis is an elusive substance with properties that may preclude straightforward generalizations." A decade later, his words are still applicable, but not necessarily to CBD.

The Safety of CBD

The first study to support the safety of CBD in humans was conducted by Mechoulam and Carlini[95] in 1978 and found no apparent toxic effects of CBD when administered to patients with epilepsy for a 3-month trial period. The safety profile of CBD was subsequently evaluated in a trial in which up to 300 mg of CBD was administered daily to patients with epilepsy and healthy volunteers for up to 4.5 months.[96]

Safety data are also available from another relatively early trial that examined the efficacy of CBD for the treatment of Huntington disease, but found no evidence of symptom relief.[97] Over the 6-week trial, there were no statistically significant differences between CBD and placebo in blood chemistry variables, blood pressure, pulse rate, and body weight. In a small 5-week study of CBD for treatment-resistant schizophrenia,[98] the investigators identified no issues with safety; however, they did not provide substantial details on how they defined "safety." Similar findings were reported in a study of bipolar patients who received up to 1200 mg of oral CBD[99]; however, the description of safety was similarly limited.

In a 3-week study in which participants were administered 10 mg of oral CBD daily,[100] there were no changes in neurologic evaluation, which included electroencephalography; cardiac evaluation, as determined by electrocardiography; psychiatric evaluation; or clinical evaluation, which included blood chemistry and urinalysis. In a 4-week trial of patients with Parkinson disease receiving up to 400 mg of CBD daily, no cognitive or motor side effects were found in the study participants.[101]

Finally, a study determined that acute CBD administration did not result in any significant toxic effects in humans, regardless of whether it was administered orally, by inhalation, or intravenously.[102] A recent systematic review determined that clinical trials have suggested that sedation is observed only with higher doses of CBD.[103]

Perhaps the greatest concern regarding the safety of CBD is its potential to cause immunosuppression. CBD may induce a biphasic response in the immune system, with higher doses potentially associated with inhibitory responses and lower doses potentially resulting in stimulatory process.[104] Thus, clinicians should be cautious when recommending CBD for patients who are immunosuppressed until further research on dosing is conducted. Other than the potential issue of immunosuppression and sedation at very high doses, there does not appear to be any other safety issues associated with CBD.[105]

Since the 1970s, we have known that CBD attenuates many of the undesirable effects of THC.[106] Of note, for those who believe that THC can be of medicinal value, its risks and side effects need to be mitigated. In recreational users, use of marijuana with high THC and low CBD concentrations has been associated with reduction of hippocampal volume, suggesting that CBD may have a role in neuroprotection.[29] A study of the role of cannabis in the development of psychosis found that CBD attenuated hippocampal volume loss, further implicating CBD in neuroprotection.[107]

In terms of psychological functioning, Rottanburg and colleagues[108] were the first to suggest that the use of marijuana with high levels of THC and low levels of CBD was associated with psychosis. Several subsequent studies have supported the role of CBD in mitigating THC-induced psychosis.[109,110,111,112]

The potential of CBD to reduce anxiety associated with the use of marijuana with high THC concentrations has also been empirically supported. Zuardi and colleagues[113] determined in 1982 that the anxiogenic effect of THC was reduced by roughly 50% when coadministered with CBD. Additional studies support the potential of CBD to mitigate THC-induced anxiety.[106,114]

However, the overall body of empirical evidence has yielded inconsistencies in the effect of CBD on THC-induced anxiety, probably owing to variance in THC/CBD ratios of marijuana used in the studies.[49] CBD has been reported to reduce the anxiety associated with cannabis withdrawal,[115] but because this finding was from a single case report, additional research is needed.

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