Medical Cannabis: where are we at?
This is a fantastic article by respected experts
Associate Professor Vicki Kotsirilos AM was Australia’s first authorised GP prescriber of medicinal cannabis in May 2018.
Professor Iain S McGregor is the Academic Director of the Lambert Initiative for Cannabinoid Therapeutics at the University of Sydney’s Brain and Mind Centre.
Extract only provided here, for the full article please scroll down below and follow the link
CANNABIS has a long history of use by humankind for fibre (eg, textile, rope, paper and fishing nets), nutrition (eg, hemp seeds and hemp seed oil), and for medicinal and spiritual purposes.
The cannabis plant is thought to contain at least 500 potentially bioactive compounds, including more than 140 that are classified as cannabinoids. The two best-known cannabinoids with medicinal properties are δ-9-tetrahydrocannabinol (THC) and cannabidiol (CBD). Other plant-derived cannabinoids (“phytocannabinoids”), such as cannabigerol (CBG), cannabinol (CBN) and cannabichromene (CBC), are of emerging interest as therapeutics. The cannabis plant also contains other chemical constituents such as terpenes and flavonoids which may contribute to the therapeutic effects of whole plant extracts. There are more than 750 different genetic strains (“cultivars”) of cannabis with different cultivars exhibiting highly variable cannabinoid and terpene content. Cultivars of the “hemp” variety of cannabis tend to be low in THC and high in CBD.
Phytocannabinoids interact with the endocannabinoid system, which is a ubiquitous signalling system found throughout the brain and body of most animal species. Components of this system include cannabinoid receptors (eg, CB1 and CB2), other non-cannabinoid receptors (eg, GPR55, GPR18, PPAR-γ, TRPV1, TRPA1), a variety of lipid signalling molecules known as “endocannabinoids” (eg, anandamide and 2-AG) and various enzymes that regulate endocannabinoid concentrations. This recently discovered system has a major influence on health and disease, and phytocannabinoids appear to have privileged access to the components of the endocannabinoid system enabling a significant modulatory effect on physiological and pathological processes.
THC, the principal intoxicating ingredient in cannabis, acts as a weak partial agonist at CB1 and CB2 cannabinoid receptors. THC affects pain processes, appetite, digestion, motor function, mood, inflammation and cognitive function. As a therapeutic drug, THC has proven utility for reduction of pain (analgesic), nausea and vomiting (antiemetic), spasticity and spasm (muscle relaxant), and as a sleep enhancer and appetite stimulant.
The side effects of THC become more prominent with higher doses and include dizziness, appetite stimulation, mild cognitive impairment, and anxiety in susceptible individuals. Exacerbation of impairment can be seen when THC is combined with alcohol or other sedatives. Caution must be exercised when driving while using THC, as deficits in attention and concentration are evident (here and here) for several hours after higher doses of THC. Medical use of THC does not currently provide a defence against current drug driving laws in Australia which prohibit the presence of THC in saliva or blood.
The Therapeutic Goods Administration (TGA) lists a range of potential side effects and precautions with the use of medicinal cannabis products, with CBD products being generally safer than THC products. A summary of relevant drug interactions can be found here for THC and CBD.
CBD is a non-intoxicating component of cannabis that has a multitude of pharmacological actions. It does not activate CB1 receptors and therefore lacks the distinctive euphorigenic and intoxicant effects of THC. Products containing CBD only are generally safe (here and here) and associated with far fewer adverse events than THC-containing products
The therapeutic applications of CBD are still under investigation, with numerous clinical trials currently underway across a wide spectrum of conditions. Anticonvulsant and anxiety-reducing effects of CBD are well documented in recent clinical trials. Other emerging properties include analgesic, anti-inflammatory, antipsychotic and anti-addiction effects. CBD can sometimes reduce side effects of THC (eg, anxiety) and is often combined with THC in medicinal cannabis products for this reason. CBD may also be of benefit in autoimmune conditions including graft-versus-host disease.
While CBD is generally well tolerated even at high doses, a possible concern relates to drug–drug interactions. As an inhibitor of certain cytochrome P450 enzymes (eg, CYP3A4, CYP2C19 and CYP2C9), CBD can increase blood concentrations of other drugs that are substrates for these enzymes, such as clobazam and citalopram, possibly increasing side effects attributable to these drugs. CBD is thought to be safe in relation to driving and is not subject to interdiction under current Australian laws.