Cannabis (Marijuana)

 

Terminology:

Cannabis: agreed international term

Marijuana: term used in the USA, particularly in relation to law

Drug Class:

Cannabinoid

Background:

Cannabis or marijuana is a plant. There are two primary classifications. These are Cannabis Indica and Cannabis Sativa. There is also a third classification called Cannabis Ruderalis. Hemp (which contains less than 0.3% THC) is a type of Cannabis Sativa and some argue that Cannabis Ruderalis is a type of Cannabis Sativa as well.

These plants contain many different chemicals called cannabinoids. The most commonly discussed cannabinoids are THC and CBD. The plant converts CBD to THC as it reaches its floral peak and this is how different ratios of CBD to THC can be achieved. THC is a psychoactive chemical whereas CBD is minimally psychoactive and has other uses.

These chemicals bind to receptors that are naturally found in the body. For example, THC binds to receptors in the body called CB1-R and CB2-R. It is an agonist at those binding sites.

Receptor type 1: Accounts for euphoric and psychological effects of cannabis and is located primarily in the CNS

Receptor type 2:  Modulates immune function, utility in pain and is widespread (but also in CNS)

The concentration of cannabinoid receptors varies depending on the part of the brain. The hippocampus is involved in the formation of new memories. There is a high concentration of cannabinoid receptors here so cannabis can affect memory formation. The cerebellum and basal ganglia help to coordinate and fine-tune movements. There is also a high concentration of cannabinoid receptors here so cannabis can affect coordination. There are no cannabinoid receptors located on the brain stem, which is critical for breathing. This is why people say that it is virtually impossible to overdose of cannabis because it will not suppress breathing.

History:

Cannabis has been a part of human history for quite some time. THC has been found in the remains of a mummy from 950 BC. Cultivation records exist from China from 28 BC. In 1545, the Spanish brought cannabis to the new world.¹

Fast forward to more recently. In the 1920s, prohibition started. People started looking for other substances and cannabis began to grow in popularity. Then, in the 1930s the great depression made people look for someone to blame for their misfortune. Mexican immigrants and their habits, like cannabis use, took some of that blame. The term “marijuana” was introduced to “Mexicanize” the word cannabis. In the 1950s you could go to prison for 2-10 years for possession. In the 1970s it was classified as a schedule 1 drug which means that the government classified it as having no medical use.

But then things have begun to change. In 1973, Oregon became the first state to decriminalize cannabis. In 1975, Alaska’s right to privacy included possessing small amounts of cannabis. In 1996, California legalized medical marijuana. Colorado and Washington then voted to legalize recreational cannabis in 2012 and sales began in 2014.

Side effects:

Headache, dizziness, drowsiness, dry mouth, paranoid thinking. Smoking cannabis can cause a significant increase in heart rate 10 minutes to 3 hours after smoking. This can lead to a 4.8 fold increase risk of myocardial infarction (heart attack) within the first hour after smoking.² The chronic use of cannabis can cause abnormal menstruation and sexual dysfunction.

Safety:

Possibly unsafe when cannabis is inhaled. In one study from New Zealand, lung cancer was increased by 8% for each joint-year of smoking³ but another study of over 4,000 patients did not show this association.⁴

Drug interactions: Cannabis can change the activity of certain substrates in the liver that process medications. For example, cannabis can induce CYP2E1, which could decrease the level of certain anesthetics and acetaminophen. Cannabis can inhibit CYP3A4 and increase the drug levels of lovastatin, cyclosporin, diltiazem, estrogens and more. Cannabis may augment thrombolytic medications as well and increase the risk of bleeding.

How effective is it:

5. A study reviewed 4,400 survey responses that recruited depressed patients and marijuana users. Never-users were compared to those who consumed marijuana daily and those who consumed marijuana once per week or less. The Center for Epidemiologic Studies Depression scale (CES-D) was used to determine the severity of depression. The weekly or less users reported the lowest levels of depression, followed by the daily users, which was followed by the never users.

6. A study analyzed data from a free app called, “Strainprint”. This app allows users to track their medical cannabis use and also to track medical condition symptoms and symptom reductions. Data was collected from 1,399 medical cannabis users who used the app a total of 18,392 times. Users perceived a 50% reduction in depression and a 58% reduction in anxiety and stress. The users of the app are also able to record which strain and which THC or CBD concentration helped their symptoms. The greatest reductions in depression were noted after using cannabis with relatively low THC and relatively high CBD. Dose did not have a large impact on treating depression either. Users reported similar reductions in depression with 1 all the way through 10 plus puffs.

7. A study looked at data on suicides from the National Center of Health Statistics Mortality Detail Files. Population analysis reveals that the legalization of medical marijuana is associated with a 5% decrease in the suicide rate. Within younger males, that number is increased. There is an 11% decrease in 20-29 year-old males and a 9% decrease in the suicide rate of 30-39 year-old males. There is little evidence that suicide is decreased for females under 40 in the states that legalized marijuana and only a small decrease in older females. The study also warns that “The exact mechanism through which suicides are reduced remains a topic for future study.”

Not all studies show positive results though

8. A study from Australia followed patients from birth to 21 years of age. Those who had started using cannabis before the age of 15 and used it frequently at 21 years were more likely to report symptoms of anxiety and depression. This was seen after adjusting for confounding factors such as gender, maternal marital status, family income, maternal mental health. This relationship was seen in similar magnitudes those who used cannabis alone as compared to those who had used cannabis and other illicit drugs.

9. A meta-analysis reviewed 14 articles of longitudinal studies that looked to see if an association between depression and cannabis use could be seen. The odds ratio for cannabis users developing depression compared with controls was 1.17. This means that they had a 17% higher risk. The odds ratio of heavy cannabis users developing depression as compared to controls was 1.62. This means that they had a 62% higher risk.  Heavy cannabis use was defined as meeting the criteria for cannabis use disorder or by using cannabis at least weekly.

References:

1. Kuhn C, Swartzwelder S, Wilson W. Buzzed. Fourth Edition. W.W Norton and company.
2. Mittleman M, Lewis R, Maclure M, et al. Triggering myocardial infarction by marijuana. Circulation. 2001 Jun 12;103(23):2805-9.
3. Aldington S, Harwood M, Cox B, et al. Cannabis use and risk of lung cancer: a case-control study. Eur Respir J. 2008 Feb;31(2):280-6.
4. Zhang LR1, Morgenstern H, Greenland S, et al. Cannabis smoking and lung cancer risk: Pooled analysis in the International Lung Cancer Consortium. Int J Cancer. 2015 Feb 15;136(4):894-903.
5. Denson T, Earleywine M. Decreased depression in marijuana users. Addict Behav. 2006 Apr;31(4):738-42. Epub 2005 Jun 20.
6. Cuttler C, Spradlin A, McLaughlin R. A naturalistic examination of the perceived effects of cannabis on negative affect. Journal of Affective Disorders, Volume 235, 1 August 2018, 198-205.
7. Anderson et al. High on Life? Medical Marijuana Laws and Suicide. IZA (Institute for the Study of Labor – Bonn, Germany) Discussion Paper No. 6280, January 2012.
8. Hayatbakhsh M, Najman J, Jamrozik K, et al. Cannabis and anxiety and depression in young adults: a large prospective study. J Am Acad Child Adolesc Psychiatry. 2007 Mar;46(3):408-17.
9. Lev-Ran S, Roerecke M, Le Foll, et al. The association between cannabis use and depression: a systematic review and meta-analysis of longitudinal studies. Psychol Med. 2014 Mar;44(4):797-810.