Can CBD temper Parkinson's-related psychosis? UK researchers will look for answers in PhII study
Cannabidiol (CBD), the cannabinoid compound found in the cannabis plant, has been tried and tested in patients with rare forms of epilepsy, inspiring the approval of GW Pharma’s $GWPH landmark plant-derived Epidiolex. Its resurgence in research — and its ubiquitous presence in oils, creams, and gummy bears — is on the basis that it is not addictive, like its intoxicating cousin THC, and retains the therapeutic potential for a plant that was once touted as a cure-all in India. Researchers at King’s College London have been studying the effect of CBD on psychosis, and on Monday signaled they are prepping to begin a large-scale Phase II trial in patients with Parkinson’s-related psychosis, characterized by hallucinations and delusions.
The research team, led by Professor Sagnik Bhattacharyya from the Institute of Psychiatry, Psychology & Neuroscience, will assess the safety and effectiveness of CBD by tracking psychotic, motor and non-motor symptoms, alongside brain imaging.
The emergence of dopamine D2 receptor antagonists in the 1950s transformed the treatment of psychotic disorders — and they persist as one of the main tools in the treatment arsenal for psychosis. However, traditional antipsychotics carry a litany of side effects and a significant proportion of patients do not derive adequate benefit from the class of drugs.
CBD casts a wide net because it acts through endocannabinoid receptors; CB1 and CB2, as well as other receptors, such as GPR18, GPR55, GPR 119, 5HT1A, and TRPV2. This suggests therapeutic value in a plethora of conditions due to its neuroprotective and immunomodulatory properties.
Preclinical studies suggest CBD may have antipsychotic properties, although cannabis use, in general, is associated with an increased risk of developing psychosis. Bhattacharyya, of King’s College London, has been unpacking the evidence supporting CBD’s benefit in psychosis patients.
In a study published last year, Bhattacharyya et al investigated the neurocognitive mechanisms that underlie the purported therapeutic effects of CBD in psychosis in a small placebo-controlled trial (n=16 participants with a clinical high risk (CHR) of psychosis received a single oral dose of 600 mg of CBD; n=17 such participants received a placebo, and n=19 control participants were not given any drug). Each participant was then studied using functional magnetic resonance imaging while performing a verbal learning task. The researchers found that CBD could partially normalize alterations in parahippocampal, striatal, and midbrain function associated with the CHR state.
Now, with a $1.2 million grant from Parkinson’s UK, Bhattacharyya will lead the Parkinson’s study, scheduled to start in early 2020. There are currently 145,000 people living with Parkinson’s in the United Kingdom, and data suggest more than half will suffer from psychosis at some point.
The trial will begin with a six-week pilot to assess the safety, tolerability, and effectiveness of pharmaceutical-grade CBD in patients with Parkinson’s-related psychosis.
CBD will be delivered orally in capsules at a dose of up to 1,000 mg/day — in a bid to find an optimum dose. In the second tranche of the study, 120 patients will be recruited to a 12-week double-blind, placebo-controlled study.
Recently, there was one antipsychotic approved for Parkinson’s disease psychosis, which is designed to work by interacting with 5HT2A receptors and to a lesser extent 5HT2C receptors — instead of targeting the overproduction of dopamine.
Acadia’s $ACAD Nuplazid was approved in 2016, although an independent panel to the FDA suggested its efficacy was not as robust as it would have liked. It was also approved with a black box warning — which most antipsychotics carry — highlighting the higher risk of death associated with its use in the elderly.
Nuplazid, which generated sales of about $146 million in the first half of this year, gained notoriety after a series of reports suggested its maker had misrepresented the dangers of using the drug and employed questionable tactics to market it, prompting an FDA review, which eventually reaffirmed the drug’s safety profile.