Early Phase in the Development of Cannabidiol as a Treatment for Addiction: Opioid Relapse Takes Initial Center Stage

Abstract

Multiple cannabinoids derived from the marijuana plant have potential therapeutic benefits but most have not been well investigated, despite the widespread legalization of medical marijuana in the USA and other countries. Therapeutic indications will depend on determinations as to which of the multiple cannabinoids, and other biologically active chemicals that are present in the marijuana plant, can be developed to treat specific symptoms and/or diseases. Such insights are particularly critical for addiction disorders, where different phytocannabinoids appear to induce opposing actions that can confound the development of treatment interventions. Whereas Δ 9 -tetracannabinol has been well documented to be rewarding and to enhance sensitivity to other drugs, cannabidiol (CBD), in contrast, appears to have low reinforcing properties with limited abuse potential and to inhibit drug-seeking behavior. Other considerations such as CBD's anxiolytic properties and minimal adverse side effects also support its potential viability as a treatment option for a variety of symptoms associated with drug addiction. However, significant research is still needed as CBD investigations published to date primarily relate to its effects on opioid drugs, and CBD's efficacy at different phases of the abuse cycle for different classes of addictive substances remain largely understudied. Our paper provides an overview of preclinical animal and human clinical investigations, and presents preliminary clinical data that collectively sets a strong foundation in support of the further exploration of CBD as a therapeutic intervention against opioid relapse. As the legal landscape for medical marijuana unfolds, it is important to distinguish it from Bmedical CBD^and other specific cannabinoids, that can more appropriately be used to maximize the medicinal potential of the marijuana plant.

The role of medical cannabis in the opioid crisis

“…THC is the most abundant compound in cannabis and the sole molecule with psychoactive effects. 14,19 As a partial agonist of the CB1 receptor, THC produces effects such as euphoria, decreased pain response, and tachycardia. 20,21 Synthetic THC and its analogues have been used as antiemetics, appetite stimulants, and neuropathic pain relievers.…”

“…28 Preliminary studies show that CBD can help prevent opioid relapse, modulate drug-seeking behaviours, and improve abstinence. 18,19 However, these investigations use purified CBD or nabiximol, an oral spray containing cannabis extract. It is not yet known whether cannabis consumption will produce similar effects.…”

MicroRNA let-7d is a target of cannabinoid CB 1 receptor and controls cannabinoid signaling

“…In fact, a randomized, double-blind, placebo-controlled, phase III trial has shown that cannabinoids may be useful add-on analgesic drugs for patients with opioid-refractory cancer pain (Portenoy et al, 2012). Although more exhaustive follow-on controlled human studies are indeed necessary, this evidence strongly supports that cannabinoids might be combined with opioids for benefiting patients with pain -and perhaps other diseases (Bisaga et al, 2015;Hurd et al, 2015).…”

Could cannabidiol play a role in the treatment of chronic pain?

“…CBD reduces morphinewithdrawal symptoms and reduces abstinence scores to a greater extent than THC alone, even in combination with THC [14]. In contrast to THC that potentiates heroin self-administration in rats, repeated CBD administration (5-20 mg/kg) did not alter heroin self-administration, but clearly inhibited cue-induced heroin-seeking behaviour with a prolonged effect, lasting two or more weeks after administration.…”