COMMENTARY

Medical Marijuana: The State of the Science

Michael E. Schatman, PhD

Disclosures

February 06, 2015

In This Article

What to Make of the "Evidence" for CBD Efficacy

Although some clinical evidence supports the use of CBD, critics are accurate in their assessment that the vast majority of compelling empirical literature, at least at present, is derived from the copious body of animal and human cell line studies. As mentioned by several literature reviews, CBD is very promising as therapy in a variety of difficult-to-treat conditions. The available evidence on the efficacy of CBD needs to be considered in conjunction with its exceptional safety profile, which has been well established in clinical trials.

The standard treatments for many conditions have largely been minimally effective or associated with significant safety and tolerability issues that affect adherence. The issue of adherence was well documented in a historical cohort study that found suboptimal adherence to Parkinson disease medications in 67% of patients.[146] Nonadherence may be even more problematic in the treatment of serious mental illness: A study comparing several antipsychotic medications demonstrated an overall 74% discontinuation rate.[147] Furthermore, although we cannot yet claim that CBD is the cure for cancer, nonadherence to chemotherapy due to its devastating side effects may result in avoidable mortality.[148]

Compared with standard treatments for many chronic diseases, the likelihood of problematic side effects or adverse events associated with CBD is small, and discontinuation in clinical studies is uncommon. In addition, given the anxiolysis associated with CBD, its use as an adjuvant therapy may mitigate many common side effects that are actually anxiety responses.

CBD as an Adjuvant Treatment

Unfortunately, data from clinical trials on the utilization of CBD as an adjuvant therapy are scarce. However, in numerous preclinical studies, CBD has been found to have synergistic and additive effects with different treatments.

For example, intranasal CBD administered with glatiramer acetate has been found to improve experimental autoimmune encephalomyelitis, an animal model of multiple sclerosis, thereby potentially offering better treatment.[149] In one of few studies conducted on cannabidiolic acid (a potent precursor of CBD), its addition to the dopamine antagonist metoclopramide resulted in a further reduction of nausea-induced conditioned gaping, suggesting a potential benefit as an adjuvant to antiemetics.[150]

The potential of CBD as an adjuvant to antiepileptic drugs was supported in a preclinical study from 1977 in which CBD increased the anticonvulsant effects of phenytoin.[151] Recently, a seminal study found that CBD in combination with morphine produced a synergistic effect to reduce chemically induced nociceptive pain, suggesting that CBD may have promise as an opioid-sparing agent.[152]

Perhaps the most exciting potential for CBD as an adjuvant therapy has been in preclinical research on cancer and complications of chemotherapy. A study found that CBD in conjunction with temozolomide produced a strong antitumor response in both temozolomide-sensitive and temozolomide-resistant tumors.[153] Recently, Ward and colleagues[154] found that CBD is effective in inhibiting paclitaxel-induced neuropathic pain while producing additive effects to synergistic inhibition of breast cancer cell viability; an earlier study suggested that CBD prevents the development of paclitaxel-induced allodynia.[155] These findings are important because they suggest that CBD can be effective in preventing chemotherapy-induced peripheral neuropathy, which affects as many as 64% of patients receiving chemotherapy.[156]

Another recent study found a synergistic effect between CBD and bortezomib in arresting cell-cycle progression and inducing cell death in multiple myeloma cell lines.[157] Of note, CBD was determined to increase drug uptake of multiple chemotherapeutic agents, potentiating cytotoxic activity in human glioma cells.[158] Another human cell line experiment determined that CBD enhanced the proapoptotic effects of bicalutamide and docetaxel, two drugs frequently used to treat prostate cancer.[159] CBD also appears to have a potential role in protecting against chemotherapy-induced cardiotoxicity, with preclinical research indicating that it ameliorates doxorubicin-induced cardiac injury.[160]

Given these and similar findings in preclinical research, the initiation of clinical trials to evaluate the safety and efficacy of adjuvant CBD in the treatment of patients with cancer is anticipated.

CBD has also been evaluated as an adjuvant treatment for psychiatric conditions. Gomes and colleagues[161] demonstrated that CBD attenuated catalepsy induced by haloperidol, suggesting its potential as an adjuvant in the treatment of psychotic disorders. Recently, a study demonstrated that dual-step administration of the partial NMDA agonist D-cycloserine and CBD resulted in the disruption of reconsolidation of traumatic memories,[162] suggesting implications for the treatment of post-traumatic stress disorder. When considered in conjunction with the growing body of clinical studies supporting the efficacy of CBD monotherapy, these preclinical investigations of adjuvant CBD further support the tremendous therapeutic potential of CBD for a wide variety of conditions.

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