Marijuana: It’s safety, and use in cancer, pain and psychiatric conditions

The Independent reported that the former leader of the Conservative Party, William Hague, has previously stated that the current British law is not only “inappropriate, ineffective and utterly out of date”, but that the government should look to Canada, which is on the cusp of legalising the drug for recreational use in additional to medical use.

The British Medical Journal have stated that the potential collective benefits of cannabis policy liberalisation include:

  1. Reduced law enforcement costs
  2. Improvements in the quality of the substance used
  3. In case of commercial legalisation, additional tax revenue.

It is already the fourth most used ‘drug’ behind alcohol, nicotine and caffeine, and the most popular illegal drug. In fact the drug’s widespread use means several police forces have confirmed they are beginning to stop targeting low level offenders.

But policy liberalisation might not just be of benefit for the above reasons, as a growing body of research validates the use of marijuana for a variety of healthcare problems.

There are four specific marijuana policies:

  • Prohibition: can be defined as a law that maintains the criminal status of any action related to marijuana possession, use, cultivation, sale, or distribution
  • Decriminalisation: describes policies that do not define possession for personal use or casual (nonmonetary) distribution as a criminal offense
  • Medical marijuana: Medical marijuana laws remove state penalties for the use of marijuana for medicinal purposes under specified conditions.
  • Legalisation: Legalisation removes criminal and monetary penalties for the possession, use, and supply of marijuana for recreational purposes.

Research has not yet fully assessed the consequences of legalisation. But…

What Can We Learn From Countries Who Have Legalised Marijuana?

Portugal

According to the Independent who reported on this Portugal effectively decriminalised possession of any drug in 2001, even heroin and cocaine, so long as the amount does not exceed a ten-day personal supply.

Since then:

  • Drug issues in the country have been treated more as medical concerns than a criminal justice issue.
  • HIV infections have fallen dramatically and drug-related deaths have decreased to among the lowest in the EU.
  • There are three drug overdose deaths for every 1,000,000 citizens. Comparable numbers in other countries range from 10.2 per million in the Netherlands to 44.6 per million in the UK, all the way up to 126.8 per million in Estonia. The EU average is 17.3 per million.
  • It has among the world’s lowest use of substances such as “synthetic” marijuana, “bath salts” and “spice”.

Netherlands

In the Netherlands, cannabis remains illegal, but was decriminalised for personal use in 1953.

Since 1976, the drug has been available for recreational use in coffee shops, and possession of up to five grams for personal use was decriminalised, though police may still confiscate it.

Official crime figures for the Netherlands show a downward trend:

  • Just 14% of cannabis users in the Netherlands report that other drugs are available from their usual cannabis source, compared to 52% in Sweden
  • Rates of cannabis use in the Netherlands are equivalent to or lower than those of many nearby countries (which do not have coffee shops), and are substantially lower than those of the US
  • Although the use of cannabis in the Netherlands has risen since 1976, this has been in line with wider European trends
  • Annually, the coffee shops generate an estimated 400 million euros in tax – money that would otherwise have accrued to criminal profiteers

The British Medical Journal concluded: “Cannabis policy liberalisation does not appear to result in significant changes in youths’ use, with the possible exception of legalisation for recreational purposes that requires monitoring.”

The British Medical Journal also has stated that:

there is also evidence that in the USA, the recent increase in opioid use is less marked in states that recently implemented policies liberalising cannabis regulations

But let’s hit pause, take a step back and discuss the basics of marijuana, it’s active constituents and how it works.

cannabis has been used and cultivated by mankind for at least 6000 years

A great paper can help us out here. The authors state: “Cannabis is a complex plant, with major compounds such as delta-9-tetrahydrocannabinol and cannabidiol, which have opposing effects. The discovery of its compounds has led to the further discovery of an important neurotransmitter system called the endocannabinoid system. This system is widely distributed in the brain and in the body, and is considered to be responsible for numerous significant functions.”

There are in fact over 400 chemical entities in the plant!

Different Cannabis Strains Have Different Effects

There are five varieties of medical cannabis available through pharmacies in the Netherlands and it is regulated by a branch of the government – the Office for Medicinal Cannabis.

A paper entitled “Cannabis, a complex plant: different compounds and different effects on individuals” discusses this topic. The authors mention that “What makes someone more susceptible to its negative effects is not yet known, however there are some emerging vulnerability factors, ranging from certain genes to personality characteristics.”

Before we look at marijuana as a therapeutic intervention it is important to note that:

evidence-based dosing and administration information on medical marijuana is lacking

The very first compound isolated in pure form from the plant was cannabinol. It was initially wrongly assumed to be the main active compound of the plant responsible for its psychoactive effects. The second compound found was cannabidiol (CBD) by Mechoulam and Shvo. The following year in 1964, Gaoni and Mechoulam isolated the main active compound, delta-9-tetrahydrocannabinol (d-9-THC).

Another cornerstone in cannabinoid research was the identification of the specific binding sites of d-9-THC in the brain. This system was named the ‘cannabinoid receptor system’ due to the binding affinity of d-9-THC to these receptors as a partial agonist. Shortly after, a second receptor, CB2R, was discovered.

  • CB1Rs are mainly in the brain, particularly in the substantia nigra, the basal ganglia, limbic system, hippocampus and cerebellum, but are also expressed in the peripheral nervous system, liver, thyroid, uterus, bones and testicular tissue.
  • CB2Rs are mostly expressed in immune cells, spleen and the gastrointestinal system, and to some extent in the brain and peripheral nervous system.

Interestingly, both CB1 and CB2Rs are also found in human placenta and have been shown to play a role in regulating serotonin transporter activity. Indeed further research has revealed that the endocannabinoid system also plays a significant role in various aspects of human reproduction.

Different compounds in marijuana have different actions in the human body. For example, delta-9-tetrahydrocannabinol (THC) seems to cause the “high” reported by marijuana users, and also can help relieve pain and nausea, reduce inflammation, and can act as an antioxidant. Cannabidiol (CBD) can help treat seizures, can reduce anxiety and paranoia, and can counteract the “high” caused by THC.

The Cannabis Plant

The cannabis plant has two main subspecies, Cannabis indica and Cannabis sativa, and they can be differentiated by their different physical characteristics. Indica-dominant strains are short plants with broad, dark green leaves and have higher cannabidiol content than the sativa plants in which THC content is higher. Sativa-dominant strains are usually taller and have thin leaves with a pale green colour. Due to its higher THC content, C. sativa is the preferred choice by users.

Let’s not ignore the concerns that have been discussed too.

An interesting paper entitled ‘Endocannabinoid System: A Multi-Facet Therapeutic Target‘ discusses how

“Presently, it is known that endocannabinoids has role in pathology of many disorders and they also serve “protective role” in many medical conditions. Several diseases like emesis, pain, inflammation, multiple sclerosis, anorexia, epilepsy, glaucoma, schizophrenia, cardiovascular disorders, cancer, obesity, metabolic syndrome related diseases, Parkinson’s disease, Huntington’s disease, Alzheimer’s disease and Tourette’s syndrome could possibly be treated by drugs modulating endocannabinoid system. Presently, cannabinoid receptor agonists like nabilone and dronabinol are used for reducing the chemotherapy induced vomiting. Sativex (cannabidiol and THC combination) is approved in the UK, Spain and New Zealand to treat spasticity due to multiple sclerosis. In US it is under investigation for cancer pain, another drug Epidiolex (cannabidiol) is also under investigation in US for childhood seizures.”

Marijuana And Psychosis

Cannabis is involved in approximately 50% of psychosis, schizophrenia, and schizophreniform psychosis cases

A meta analysis stated: “Current evidence shows that high levels of cannabis use increase the risk of psychotic outcomes and confirms a dose-response relationship between the level of use and the risk for psychosis. Although a causal link cannot be unequivocally established, there is sufficient evidence to justify harm reduction prevention programs.”

However a different paper concluded: “Evidence reviewed here suggests that cannabis does not in itself cause a psychosis disorder. Rather, the evidence leads us to conclude that both early use and heavy use of cannabis are more likely in individuals with a vulnerability to psychosis. The role of early and heavy cannabis use as a prodromal sign merits further examination, along with a variety of other problem behaviors (e.g., early or heavy use of cigarettes or alcohol and poor school performance).

In some studies, cannabis use was associated with more severe symptoms at baseline, increased pre-psychotic symptoms immediately after intoxication, and earlier onset of certain high-risk symptoms. In others, no significant association between cannabis use and baseline symptomatology was found. In one study, cannabis use was even significantly associated with a decrease in pre-psychotic negative symptoms, and with fewer symptoms of depression and anxiety.

Four out of 5 studies reported no significant effect of cannabis use on transition to psychosis.

The results of the current study suggest that having an increased familial morbid risk for schizophrenia may be the underlying basis for schizophrenia in cannabis users and not cannabis use by itself.

“Cannabis acts as a component cause of psychosis, that is, it increases the risk of psychosis in people with certain genetic or environmental vulnerabilities, though by itself, it is neither a sufficient nor a necessary cause of psychosis.”

The incidence of psychosis in cannabis exposed and non exposed population is 31 and 20%, respectively. Cannabis exposure may be a “component cause” which interacts with other factors that may be a possible cause of schizophrenia or other psychotic disorders, but is neither necessary nor sufficient to do so alone.

Adolescent cannabis use, childhood trauma, and increased risk of later psychosis are intricately related

However this study concluded that “although the observed effects are subtle, using high cannabidiol content cannabis was associated with significantly lower degrees of psychotic symptoms providing further support for the antipsychotic potential of cannabidiol”.

Marijuana And Cancer

A number of small studies of smoked marijuana found that it can be helpful in treating nausea and vomiting from cancer chemotherapy.

A few studies have found that inhaled (smoked or vaporized) marijuana can be hepful treatment of neuropathic pain (pain caused by damaged nerves).

Smoked marijuana has also helped improve food intake in HIV patients in studies.

Marijuana And Cardiovascular Health

Dysregulation of the endogenous lipid mediators endocannabinoids and their G-protein-coupled cannabinoid receptors 1 and 2 (CB1R and CB2R) has been implicated in a variety of cardiovascular pathologies. Activation of CB1R facilitates the development of cardiometabolic disease, whereas activation of CB2R (expressed primarily in immune cells) exerts anti-inflammatory effects. The psychoactive constituent of marijuana, THC, is an agonist of both CB1R and CB2R, and exerts its psychoactive and adverse cardiovascular effects through the activation of CB1R in the central nervous and cardiovascular systems. The past decade has seen a nearly tenfold increase in the THC content of marijuana as well as the increased availability of highly potent synthetic cannabinoids for recreational use. These changes have been accompanied by the emergence of serious adverse cardiovascular events, including myocardial infarction, cardiomyopathy, arrhythmias, stroke, and cardiac arrest.

Marijuana And Liver Health

Constituents of cannabis, such as cannabidiol and THC, have shown anti-inflammatory, antioxidant, and hepatoprotective effects both in in vitro and clinical studies, and appear to have potential in the symptom management and treatment of various liver diseases that were previously considered difficult to manage conservatively.

Marijuana and Headaches

The literature suggests that the medicinal use of cannabis may have a therapeutic role for a multitude of diseases, particularly chronic pain disorders including headache. Supporting literature suggests a role for medicinal cannabis and cannabinoids in several types of headache disorders including migraine and cluster headache, although it is primarily limited to case based, anecdotal, or laboratory-based scientific research.

Marijuana And IBD

From first surveys and small clinical studies in patients with IBD we have learned that Cannabis is frequently used to alleviate diarrhea, abdominal pain, and loss of appetite.

cannabinoids have been shown to improve intestinal inflammation in experimental models of IBD through their interaction with the endocannabinoid system. However, the few randomized controlled trials of cannabis or cannabidiol in patients with IBD have not demonstrated efficacy in modulating inflammatory disease activity. Cannabis may be effective in the symptomatic management of IBD.

Marijuana And PTSD

Cannabis has been reported as a coping tool for patients with PTSD and preliminary legalization data indicate Cannabis use may reduce the use of more harmful drugs, such as opioids. Rigorous clinical studies of Cannabis could establish whether Cannabis-based medicines can be integrated into treatment regimens for both PTSD and substance use disorder patients.

Will It Ever Be Legalised?

This paper lays out recommendations for legal cannabis regulations that could mitigate this harm.

Whilst a lot of evidence would suggest that the concern is still too great to legalise cannabis in the UK. A group of cross-party MPs (Labours David Lammy, Conservative Jonathan Djanogly and LibDem Sir Norman Lamb) who travelled to Canada where it is legal have predicted that the UK will fully legalise cannabis use within five to ten years.

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