Graft-versus-host disease (GVHD) is a common â€“ and potentially fatal â€“ complication following bone marrow and solid organ transplants. This life threatening condition can also occur after a patient receives a blood transfusion or other forms of transplanted tissue from a genetically differentÂ person.
The mortality rate for acute GVHD is over 80 percent. And there are no reliable molecular markers that indicate the onset or reflect the severity of a post-transplant reaction. Currently there are no FDA-approved therapies for this disease. The ability to treat acute GVHD is thus a major unmet medicalÂ need.
But hope is on the horizon, thanks to cannabidiol (CBD), a non-intoxicating component of cannabis, according to a team of Israeli scientists at the Rabin Medical Center. Data from three phase 2 clinical studies in Israel showed dramatic results when 150 mg of pure CBD was orally administered twice daily to ten patients with acute GVHD who did not respond to steroids. Although the sample size was small, the outcome proved noteworthy: â€śConsumption was safe and no significant adverse effects were reported. Nine out of ten patients responded to treatment, seven of them achieved complete remission and two achieved very good partialÂ response.â€ť
The Israeli study, â€śCannabidiol â€“ An innovative strategy for the treatment of graft versus host disease,â€ś was featured on Day One of the 2018 International Cannabinoid Research Society conference, which convened this summer in the picturesque Dutch city of Leiden. Over 500 delegates from around the world attended the annual four-day gathering, where they discussed cutting-edge developments in cannabis science andÂ medicine.
This yearâ€™s ICRS conference featured 58 oral presentations, including four keynotes, and 235 posters that covered a wide range of topics. CBD figured prominently in many of these reports, which also explored the health benefits of tetrahydrocannabinol (THC) and other plant cannabinoids. But the main focus, as always, was on the endocannabinoid system itself, which mediates many of the effects ofÂ cannabis.
Andras Bilkei-Gorzo, a University of Bonn scientist, linked brain aging to a decline in activity of the endocannabinoid system (characterized by diminished endocannabinoid levels and reduced coupling with CB1 cannabinoid receptors). But animal models showed that normal, age-related, cognitive decline can be counteracted with a chronic low dose of THC: â€śMost strikingly, THC treatment facilitated a rebalanced hippocampal gene transcription in old mice so that their expression profiles closely resembled that of young THC-free animals â€¦ Thus, restoration of CB1 signaling in old individuals could be an effective strategy to treat or prevent age-related cognitiveÂ impairments.â€ť
The neuroprotective properties of plant cannabinoids were noted in several other presentations at ICRSÂ 2018:
Clara Andradas, a medical scientist at the Telethon Kids Institute in Western Australia, has been researching potential applications of cannabinoids for treating pediatric cancer, specifically malignant brain tumors. Her poster disclosed that CBD and THC reduced the viability of brain cancer cells, an effect mediated in part by the CB2 cannabinoid receptor. Moreover, â€śthe combination of cannabinoids with conventional chemotherapies enhances the anti-proliferative effects in these cells,â€ť sheÂ concluded.
Temple University scientists assessed the therapeutic impact of CBD combined with beta-caryophyllene (BCP), a versatile terpene present in many cannabis cultivars, kitchen spices, and green vegetables. Unlike cannabidiol, BCP directly activates the CB2 receptor, which modulates immune function and neuroprotection in response to brain trauma. The two compounds together â€śshowed a statistically significant reduction in infarct size,â€ť according to the investigators, who concluded that â€ścombination therapies can provide a greater benefit than single treatments aloneâ€ť and should be explored further for treating ischemic stroke and otherÂ diseases.
Mark Lewis, a plant scientist with Napro Research in California, provided additional evidence that whole plant cannabis medicine may be more efficacious than pure, single-molecule cannabinoids. Lewis has bred several CBD-rich and BCP-rich cannabis chemovars. In vitro analysis showed that various CBD–BCP ratios inhibited cellular inflammation. Co-administration of CBD and BCP â€śproduced enhanced effects as compared to each compound alone.â€ť Of particular interest, the anti-inflammatory impact â€śproduced by certain CBD concentrations increased by up to ten times when co-administered with certain concentrations of BCP.â€ť
Anecdotal accounts from cannabis consumers attest to the benefits of artisanal, terpene-rich remedies. Whistler Therapeutics, a boutique medical marijuana company in British Columbia, surveyed Canadian patients to assess the analgesic impact of different aromatic terpenes in cannabis. Imbued with their own medicinal properties, terpenes interact synergistically with CBD, THC and other plant cannabinoids. For pain management purposes, the best results were obtained using cannabis varietals with noteworthy concentrations of myrcene andÂ trans-nerolidol.
Part 2. Â ICRS 2018: Report from Leiden â€“ â€śTargeting the endocannabinoid system for therapeuticÂ reliefâ€ť
Project CBD director Martin A. Lee is the author of Smoke Signals: A Social History of Marijuana â€“ Medical, Recreational and Scientific.