The current state of research into pharmaceutical applications for cannabis and its extracts

By Louise Saul, Scientific Writer

Scientific interest in cannabis and the products isolated from it is growing rapidly due to the potential medical applications of these substances, partially boosted by the easing of restrictions for both the use and possession of the drug, but there is still much debate about the legal and ethical implications of using cannabis to treat illness and disease. Louise Saul reports.

The analysis of cannabis is a growing area of research at the moment due to the vast range of possibilities for both recreational and medical use of the plant and its extracts. As well as the well-known psychoactive substance tetrahydrocannabinol (THC) and non-psychoactive cannabidiol (CBD) found in the plant, cannabis itself also contains more than 100 different cannabinoids that can be isolated. The popularity of cannabis and the products isolated from it grows every year due to the potential medical applications and the loosening of restrictions for both its use and possession, but there is still much controversy surrounding the legal and ethical implications of using cannabis to treat illness and disease.

Cannabinoids: possible application areas

Cannabinoids can be split into phytocannabinoids, endocannabinoids and synthetic cannabinoids. Cannabinoids work by acting on the endocannabinoid system. They target the cannabinoid receptors CB1 and CB2 by activating G-proteins, which function as signalling and regulatory proteins. CBD1 receptors are found in the central and peripheral nervous system, whereas CBD2 receptors are found in the brain, but are primarily located in the immune system.

The industries interested in analytical cannabis include the pharmaceutical, food and tobacco sectors. Cannabis itself can be smoked, vaped, be a component in food and also be used as an extract.The term medical marijuana is often used, but this actually refers to areas of medicine and research where it is thought that cannabis can be beneficial.

The pharmacokinetics and pharmacodynamics of THC is much better understood than those of CBD, but due to the psychoactive nature of THC, the current main compounds of interest in cannabis research are CBD and its metabolites. THC is already used as an anti-vomiting drug in cancer and as an appetite stimulant for AIDS patients, but there is much ongoing research into the effectiveness of CBD as a treatment for a number of diseases, including as a treatment for seizures, pain, anxiety and cancer. Cannabichromene (CBC) is also an area of interest due to its showing anti-inflammatory, anti-fungal and anti-microbial activities.

CBD in neurology

The use of CBD as a pain treatment covers a lot of disease areas, including chronic pain and cancer. The endocannabinoid system itself plays a role in the control of pain, and cannabinoids target that system. There are many unregulated products that claim to contain CBD, which has contributed to much CBD fraud on the high street, while these same CBD oils and supplements are being used to treat anxiety dangerously. The only CBD drug currently approved by the FDA is Epidiolex, which was also approved for use in the UK this year. The drug is used to treat epilepsy seizures, and its approval has opened up many possibilities for treating the other illnesses in which it may be effective.

Both THC and CBD are being looked into in preclinical studies as ways of treating neurodegenerative diseases such as Parkinson’s disease, Alzheimer’s disease and multiple sclerosis. The cannabinoids are thought to prevent neuronal damage in Parkinson’s disease due to CBD’s anti-inflammatory and antioxidant properties. In Alzheimer’s disease, it is hypothesized that THC binds and competitively inhibits the enzyme acetylcholinesterase, as well as preventing acetylcholinesterase-induced amyloid-beta-protein aggregation. There are many theories as to how CBD acts as a neuroprotector, including reduction of oxidative stress, anti-apoptotic effects, inhibition of amyloid-beta-induced tau protein hyperphosphorylation, and a decrease in amyloid-beta production and amyloid-beta-induced neurodegeneration. With multiple sclerosis, preclinical studies have shown an improvement in the signs of motor dysfunction, but there is currently no evidence to support the use of cannabinoids over the other treatments still available.

Viral disease treatments

CBD and THC have also been shown to be effective in the treatment of viral diseases and, with viral hepatitis diseases, there is evidence that it can help in the fight against hepatitis C (HCV). HCV is one of the most dangerous of the five hepatitis types, alongside hepatitis B (HBV), but CBD has yet to be shown to be effective against HBV. In addition to HCV, CBD is the subject of research for the treatment of other viral diseases, including HIV.Even if they are given an anti-viral treatment, up to 50 per cent of people with HIV suffer from HIV-associated neurocognitive disorders (HAND). Researchers at George Mason University have been looking into using cannabinoids on infected HIV cells, with preliminary results showing a reduction in HIV-1 transcription of both short non-coding RNA and full-length genomic RNA. The reduced transcription lowers the production of the HIV-1 virus.

Treating sickle cell anaemia

In a recent clinical study at the University of California, it was shown that cannabis was a safe and effective treatment for chronic pain for people with sickle cell anaemia. The current treatment uses opioids, but there has been a rise in opioid-related deaths, so doctors were looking for alternative choices for treatment. The study was only small, with just 23 patients with sickle cell disease-related pain completing the trial, but during the two five-day inpatient sessions separated by at least 30 days, pain levels throughout the treatment period were assessed and it was found that the effectiveness of cannabis increased over time.

Potential in COVID-19 treatment

It was recently discovered that CBD might also be able to help with the current COVID-19 pandemic. COVID-19 damages the lungs, and CBD can reduce damage to the lungs due to coronavirus. CBD decreases pro-inflammatory cytokine production, as well as reducing angiotensin-converting enzyme 2 (ACE2) expression. Both the reduction of cytokine production and ACE2 expression is predicted to help with bringing down lung inflammation caused by COVID-19 and prevents further damage, but research into this is still in the very early stages.

Avoiding fraud

Alongside the research being carried out into the medical uses of cannabis, regulatory testing is important in order to avoid fraud. Types of cannabis fraud include legal products containing unlisted safe ingredients, unlisted hazardous ingredients, illegal levels of banned drugs or products that contain no cannabinoids in their extracts at all. A frequent problem with fraudulent cannabis products is the levels of heavy metals and solvents harmful to human health that are present. Products are constantly being recalled by the FDA and companies being sued over toxic contaminants in their CBD products. Chromatography, spectrometry and spectroscopy are the main analytical techniques used for the analysis of cannabis and its extracts and the detection of such contaminants.

Scope for the future

The future of analytical cannabis research is vast, with many avenues left to explore. In Europe, a new medical cannabis trial has started under the project name Twenty21. The project will last for two years and hopes to recruit up to 20,000 people in order to study how effective cannabis is as a treatment for numerous diseases, including anxiety, chronic pain, multiple sclerosis, post-traumatic stress disorder and Tourette’s syndrome. Meanwhile, in the US, the FDA recently released its new guidelines on cannabis research to help create a structure for the vastly growing cannabis industry. The FDA guideline is for cannabis and cannabis-derived compounds used in drug manufacturing, and includes include botanical raw materials, extractsand purified substances of botanical origin.