© 2017 by Shawn Wilson 

Cannabis and the Body

September 5, 2017

Photo by Esteban Lopez

 

Marijuana (cannabis) has increased in popularity in recent years, particularly as pro-legalization movements have helped passed laws in multiple states that legalize the use of cannabis or medical marijuana. As with most issues, there are proponents and opponents for cannabis use. Trying to take emotions out of the equation, it is usually a good idea to go back and see what the research says. This post will look at some of the research that examines how cannabis impacts our physical and mental health.

 

It should be noted however that unfortunately a lot of great research on cannabis use cannot yet be conducted because cannabis is classified as a Schedule I drug in the United States, similar to LSD, ecstasy, and heroin. Schedule I drugs are drugs that are considered to have a high potential for abuse, has no currently accepted medical use (with the exception of cannabis), and the drug cannot be safely used.

 

By classifying cannabis as a Schedule I drug, it is much more difficult for researchers to obtain permission from the government to conduct studies on the impact of cannabis. There have been multiple attempts to declassify cannabis as a Schedule I drug, but unfortunately thus far these attempts have been unsuccessful (side note: cocaine is classified as a less dangerous Schedule II drug). This is despite research that indicates that cannabis is less harmful and addictive than other substances including alcohol, which is of course legal in the United States.

 

There is a lot of hysteria regarding cannabis, going back to the ‘Reefer Madness’ days. The question is, what does the research really say about cannabis? First, let us cover some basics about cannabis and cannabinoids.

 

Overview of Cannabis and Cannabinoids

 

Marijuana comes from the Cannabis sativa plant, which is why marijuana is also called cannabis. Indeed, while there is not a lot of information out there about the origins of the word marijuana, it does seem that the word has a racist history.

 

For research and clinical work you see the word cannabis used more often, and in more popular mainstream sources you will more likely see the word marijuana being used. Both words refer to the same drug and so the drug will be referred to as cannabis in this post to avoid any negative connotations of the word marijuana, despite it not generally being seen as a negative word.

 

The main active chemical in cannabis is delta-9-tetrahydrocannabinol (THC). THC closely resembles a neurotransmitter called anandamide. Because of this, THC can attach itself to molecules called cannabinoid receptors, which are part of the endocannabinoid system and can be found in different parts of the brain. Specifically, areas of the brain such as the hippocampus, amygdala, cerebellum, spinal cord, nucleus accumbens, and hypothalamus have high concentrations of cannabinoid receptors. THC keeps cannabinoid receptors firing in the brain, which then causes the effects related to cannabis use.

 

Some brain areas result in some not-so-nice effects of using cannabis. For example, the hippocampus is largely responsible for processing memory and emotional responses. As such, when THC binds with the cannabinoid receptors in the hippocampus, it interferes with short-term memory. The amygdala helps us regulate our emotions and particularly fear, which is why using cannabis can cause people to feel anxiety. The cerebellum is largely responsible for our motor coordination and balance and using cannabis will cause people to have impaired coordination.

 

However, some brain areas result in more positive effects. For example, when THC attaches to receptors in the spinal cord, it reduces how much pain information is sent from the body to the brain, which has the result of reducing how much pain people feel. This is why some people use cannabis to manage migraines and other chronic pain conditions. In addition, when THC binds to receptors in the nucleus accumbens, it results in a positive, euphoria, ‘this-feels-good’ feeling.

 

Lastly, the hypothalamus controls our hunger, thirst, and sleep, amongst other functions. THC binding to receptors in the hypothalamus are what cause the ‘munchies’ sensation that accompanies cannabis use. This may not be a particularly useful effect for most people, although for individuals who experience significant nausea, such as those undergoing chemotherapy, cannabis can help stimulate appetite.

 

As previously mentioned, cannabis use has increased in recent years as laws in an increasing number of states legalize cannabis and/or medical marijuana use. A Gallup poll found that 13% of adults endorsed current cannabis use, which is up from 7% in 2013. In addition, 43% of Americans endorsed having ever tried marijuana.

 

A little more information about cannabis more broadly; it seems to be nearly impossible to overdose and die from smoking cannabis. However, one can ‘overdose’ on cannabis by using so much that a person experiences panic attacks or extreme paranoia.

 

Indeed, compared to many other drugs used recreationally, marijuana has a lower risk of harm than substances such as alcohol, tobacco, cocaine, and heroin. This is supported both with scientist rankings of relative harm of different drugs as well as research studies, such as one conducted by Lachenmeier and Rehm [1].

 Source: Wikipedia Commons, data from Nutt, King, & Philips, 2010

 

Another thing to know is that while it is not quite clear if cannabis nowadays is more potent than in the past, it does seem clear that cannabis strains vary widely in terms of their THC. Cannabis strains can range from .3% to 25% THC, which will naturally impact how the user feels from the cannabis use.

 

While THC largely is responsible for the psychoactive effects of cannabis, there is another chemical that is extremely important in understanding the impact of cannabis. This other chemical is called cannabidiol (CBD), and it is believed to be responsible for many of cannabis’s medical benefits.

 

CBD is not believed to lead to the ‘stoned’ feeling that people experience, like THC does, and instead may be responsible for making people experience less anxiety and disordered thinking. In addition, while there is not great evidence, research suggests that CBD can help prevent epilepsy and other neurological conditions.

 

So as we dive in and discuss the research regarding medical marijuana, understand that the whole cannabis plant contains cannabinoids that include both THC and CBD. This helps explain some of the mixed findings regarding the impact of cannabis on our functioning. And now, without further ado, let us look at some studies!

 

Medical Marijuana

 

A review and meta-analysis was conducted to examine how effective cannabinoids are for medical use which included 79 randomized controlled trials (RCTs) and almost 6,500 participants [2]. Specific uses of medical marijuana examined included reducing nausea and vomiting due to chemotherapy, increasing appetite in patients with HIV/AIDS, chronic pain, spasticity (involuntary muscle spasm contraction) due to multiple sclerosis, depression, anxiety, sleep problems, glaucoma, and psychosis.

 

The study found moderate evidence for cannabinoids reducing pain experienced and reducing spasticity. There was also low quality evidence supporting cannabinoids for reducing nausea and vomiting related to chemotherapy, increasing weight gain in HIV patients, improving sleep problems, and reducing tic severity related to Tourette syndrome.

 

However, using marijuana was not without risks. The study also identified adverse events related to marijuana use including: dizziness, nausea, fatigue, disorientation, drowsiness, confusion, and experiencing hallucinations.

 

Generally, the study noted that a lot of the research conducted had a high risk of bias, which makes us less confident about the results of studies. In research terms, bias means deviation from the truth. Bias can occur for a variety of reasons including not appropriately randomizing the participants, there being systematic differences between the participants at baseline, and the researchers impacting the results by knowing who is in what condition.

 

In a separate review of the efficacy of medical marijuana on neurological conditions, different findings were supported depending on the administration of the medical marijuana [3]. For example, the review examined oral cannabis extract (OCE), THC, and nabiximols (nasal spray containing THC and CBD).

 

The review found that OCE was effective for treating spasticity and central pain in those with Multiple Sclerosis (MS) and that THC and nabiximols were probably effective in treating these problems. Nabiximols were probably effective in treating urinary dysfunction in those with MS, while OCE and THC were probably ineffective at treating this problem. The review determined that OCE, THC, and nabiximols were all likely ineffective in treating MS-related tremors. 

 

In addition to these MS-specific findings, the review looked at other outcomes. The review reports that there were not any studies with sufficient rigor that demonstrates cannabinoids reduce seizure frequency. There was also not sufficient evidence to support the use of cannabinoids to reduce tics, such as ones that occur due to Tourette's syndrome.​​

 

While the review could not make a determination regarding the efficacy of medical marijuana for treating epilepsy, a separate review by Rosenberg and colleagues of cannabinoids and epilepsy states that CBD specifically appears to be a promising and well-tolerated treatment for seizures [4]. The Rosenberg review notes that cannabis (containing THC and CBD) can both contribute to and reduce seizures. The review also makes clear that there are still a lot of unanswered questions regarding cannabinoids and epilepsy, including the long-term effects of taking cannabinoids.

 

Now that we have reviewed some of the potential benefits of using cannabis, let us examine some of the concerns that people have regarding cannabis use.

 

Psychosis and Schizophrenia

 

One of the concerns regarding cannabis use is that historically people believed that cannabis use is associated with later psychosis (i.e., hallucinations, delusions). Indeed if this link does exist, it suggests that certain populations should avoid using cannabis to avoid triggering a future psychotic episode.

 

A study by Barrowclough and colleagues [5] used a sample of 110 participants with a psychotic disorder and co-occurring cannabis use disorder. Specifically the researchers were interested in ‘recent onset psychosis.’ While it is somewhat unclear from the study how recent they considered recent to be, the participants had an average history of psychotic symptoms for 18 months. These participants were assessed at baseline, 4.5 months, 9 months, and 18 months.

 

The study found that there was no relationship between cannabis use and psychotic symptoms, relapse of psychotic symptoms, or hospital admissions. However, cannabis use was associated with higher levels of anxiety. In addition, reducing cannabis use was associated with better participant functioning.

 

Contrary to the above study, a separate study longitudinally examined cannabis use in adolescence and outcomes involving psychosis with over 50,000 military conscripts over a span of 35 years [6]. Needless to say that number of participants assessed over that long of period of time is extremely impressive for a research study.

 

The researchers found that frequent cannabis use was associated with an increased chance of later having schizophrenia, brief psychosis, or another type of psychosis. For moderate users of cannabis, there was still an increased risk of later developing schizophrenia, although this risk decreased over time.

 

Of note, because heavy cannabis use was more strongly related to developing schizophrenia, the researchers state that the study supports a dose-response association between cannabis use and schizophrenia. This means that the there is a direct relationship between how much cannabis is used and one’s risk of developing schizophrenia. What would be interesting to examine is if there is a safe level of cannabis use that does not lead to later psychotic symptoms.

 

So really it seems that there is still some confusion regarding the role that cannabis plays in the development of psychosis and related disorders. Since schizophrenia has a very strong biological basis, it does not seem likely that cannabis will cause random cannabis users to develop schizophrenia. Instead, heavy cannabis use may serve as an environmental trigger that makes it more likely that someone already at risk for schizophrenia goes on to develop the condition.

 

If this finding is supported, then it suggests that there are certain people who really would be better off never using cannabis, particularly if they have family members who have been diagnosed with schizophrenia.

 

So overall, it does appear that there is a risk of cannabis use triggering psychosis in individuals, although the timing of this relationship needs clarification. As previously mentioned, THC and CBD can have opposite effects and CBD does appear to inhibit psychotic symptoms, whereas THC appears to make psychotic symptoms worse [7]. Therefore, the THC and CBD content of the cannabis used also likely impacts the development of psychotic symptoms.

 

Prenatal Cannabis Use

 

As cannabis use increases, another important question is how does prenatal cannabis use impact a developing fetus? We know that prenatal exposure to substances such as alcohol and cigarettes is bad, but how is a fetus impacted by maternal cannabis use?

 

A review and meta-analysis of research examining prenatal exposure to cannabis was conducted by Gunn and colleagues [8]. Results of the meta-analysis found that women who used cannabis during their pregnancy had a higher risk of anemia. In addition, infants exposed to cannabis in utero had lower birth weights compared to infants who were not exposed to cannabis in utero. Infants who were exposed to cannabis in utero were also more likely to need placement in a neonatal intensive care unit (NICU).

 

One of the major drawbacks of the research conducted to date is that most mothers who use cannabis during their pregnancy are also using other substances, such as alcohol and tobacco. Naturally this makes it difficult/impossible to determine what the impact is of using only cannabis on prenatal development. Given this significant limitation, it is clear that more research is needed on this topic. That being said, preliminary results indicate there are negative outcomes for both the mother and the fetus related to prenatal cannabis use and there does not currently seem to be any support for cannabis use during a pregnancy.​

 

Cannabis Use Amongst Youth

 

Another major concerns about cannabis use is how it impacts youth development. In particular, you often hear about how cannabis use during adolescence permanently changes adolescents’ brain structures. Let us take a look at what research has found in terms of outcomes for adolescent cannabis use.  

 

A review was conducted by Copeland and colleagues [9] to examine recent trends of cannabis use amongst youth. What this review found was that cannabis use predicts the development of later anxiety disorders, major depression, suicidal ideation, certain personality disorders, and interpersonal violence. These associations are stronger for adolescents compared to adults and it appears that the younger one starts to use cannabis, the greater the likelihood that person will develop a mental health problem.

 

Remembering that correlation is not causation, what is less clear is if individuals with more severe cannabis use in adolescence have more serious mental health problems because of their early cannabis use or if individuals with more serious mental health problems use cannabis to help them manage their emotions and behavior. The causal pathways appear less clear and more research is needed to clarify ways in which early cannabis use directly leads to more mental health problems, if such a relationship exists.

 

In a study that combined data from three large longitudinal studies in Australia and New Zealand, examined adolescent cannabis use and important outcomes later in life [10]. The study found that adolescents who were daily users of cannabis prior to the age of 17 had lower rates of completing high school and obtaining a degree, and had an increased likelihood of later meeting criteria for cannabis use disorder, of later using other illicit drugs, and having a suicide attempt.

 

Based on this research, it is again difficult to show direct causal relationships between cannabis use and these outcomes. That being said, it is definitely concerning that early cannabis use is associated with negative outcomes later in life and at the very least, early cannabis use can help us identify individuals in need of interventions.

 

Lastly, in a review of studies examining brain changes in chronic cannabis users, adolescent cannabis use was significantly associated with changes in the brain structure and functioning [11]. These brain changes appear to occur shortly after an adolescent starts using cannabis, last for a month post-cannabis abstinence, and appears to result in more pronounced changes for females as opposed to males.

 

In addition, the review notes that there is some indication cannabis use during adolescence interferes with the natural brain changes that occur during this developmental period called pruning. The review notes that there is a lack of quality research looking at adolescent brain changes over time in response to cannabis use.

 

Taken together, this research on adolescents appears to show that cannabis use at younger ages is associated with worse outcomes including mental health and education outcomes, as well as resulting in brain changes that last for some time after the individual stops using cannabis. Based on this research, there is definitely a concern about adolescents using cannabis, although based on a lack of quality research, it is difficult to say specifically how cannabis use leads to negative outcomes. Hopefully this can be clarified in the future.

 

Summary

 

Cannabis use is a pretty hotly debated topic these days as an increasing number of states legalize cannabis in the United States and more broadly as countries legalize medical marijuana or cannabis around the world. There are advocates on either side trying to push what they feel is right, whether it is legalization or criminalization. When emotions start to get involved and rule the debate, it is to always rely on what the research says. Research may never be perfect, but it surely provides a better guideline than basing it solely on one’s opinion.

 

The problem currently is that a lot of quality research is not being allowed to happen because of the “dangers” of cannabis. Based on the research available, this seems sorely misinformed. Truthfully, at least some individuals will always use cannabis, and so for these individuals’ benefit, we should better understand the long-term impacts of using cannabis. More research needs to be conducted so we can determine any positive or negative effects of cannabis.

 

This post did not address the social issues related to cannabis use, such as how criminalizing cannabis use disproportionately impacts minority individuals. There is a lot to be said about the societal impact of criminalizing cannabis use, which could be the topic of a separate post. This is just a quick acknowledgement that laws are not solely based on what available research states and that there are other important considerations to also weigh.

 

This post covered a lot of research regarding cannabis use. To summarize it all, there appears to be some potential benefits of medical marijuana and there are some significant negative consequences for using cannabis. While cannabis use is less risky than many other substances including alcohol and tobacco, cannabis use is not without risk.

 

Hopefully this post helped provide some information so that whoever decides to use or not use cannabis, does so with an understanding of current research related to cannabis. It is always best to be informed in our decision making, particularly with things that can impact our health and well-being.
 

References

 

[1] Lachenmeier, D. W., & Rehm, J. (2015). Comparative risk assessment of alcohol, tobacco, cannabis and other illicit drugs using the margin of exposure approach. Scientific Reports, 5(1), 1-7. doi:10.1038/srep08126

 

[2] Whiting, P. F., Wolff, R. F., Deshpande, S., Di Nisio, M., Duffy, S., Hernandez, A. V., ... & Schmidlkofer, S. (2015). Cannabinoids for medical use: A systematic review and meta-analysis. Journal of the American Medical Association, 313(24), 2456-2473. doi:10.1001/jama.2015.6358

 

[3] Koppel, B. S., Brust, J. C., Fife, T., Bronstein, J., Youssof, S., Gronseth, G., & Gloss, D. (2014). Systematic review: Efficacy and safety of medical marijuana in selected neurologic disorders: Report of the Guideline Development Subcommittee of the American Academy of Neurology. Neurology, 82(17), 1556-1563. doi:10.1212/wnl.0000000000000363

 

[4] Rosenberg, E. C., Tsien, R. W., Whalley, B. J., & Devinsky, O. (2015). Cannabinoids and Epilepsy. Neurotherapeutics, 12(4), 747-768. doi:10.1007/s13311-015-0375-5

 

[5] Barrowclough, C., Gregg, L., Lobban, F., Bucci, S., & Emsley, R. (2014). The impact of cannabis use on clinical outcomes in recent onset psychosis. Schizophrenia Bulletin, 41(2), 382-390. doi:10.1093/schbul/sbu095

 

[6] Manrique-Garcia, E., Zammit, S., Dalman, C., Hemmingsson, T., Andreasson, S., & Allebeck, P. (2011). Cannabis, schizophrenia and other non-affective psychoses: 35 years of follow-up of a population-based cohort. Psychological Medicine, 42(06), 1321-1328. doi:10.1017/s0033291711002078

 

[7] Bhattacharyya, S., Morrison, P. D., Fusar-Poli, P., Martin-Santos, R., Borgwardt, S., Winton-Brown, T., . . . McGuire, P. K. (2009). Opposite effects of Δ-9-tetrahydrocannabinol and cannabidiol on human brain function and psychopathology. Neuropsychopharmacology, 35(3), 764-774. doi:10.1038/npp.2009.184

 

[8] Gunn, J. K., Rosales, C. B., Center, K. E., Nuñez, A., Gibson, S. J., Christ, C., & Ehiri, J. E. (2016). Prenatal exposure to cannabis and maternal and child health outcomes: A systematic review and meta-analysis. BMJ Open, 6(4). doi:10.1136/bmjopen-2015-009986

 

[9] Copeland, J., Rooke, S., & Swift, W. (2013). Changes in cannabis use among young people. Current Opinion in Psychiatry, 26(4), 325-329. doi:10.1097/yco.0b013e328361eae5

 

[10] Silins, E., Horwood, L. J., Patton, G. C., Fergusson, D. M., Olsson, C. A., Hutchinson, D. M., . . . Mattick, R. P. (2014). Young adult sequelae of adolescent cannabis use: An integrative analysis. The Lancet Psychiatry, 1(4), 286-293. doi:10.1016/s2215-0366(14)70307-4

 

[11] Batalla, A., Bhattacharyya, S., Yücel, M., Fusar-Poli, P., Crippa, J. A., Nogué, S., . . . Martin-Santos, R. (2013). Structural and functional imaging studies in chronic cannabis users: A systematic review of adolescent and adult findings. PLOS ONE, 8(2), e55821. doi:10.1371/journal.pone.0055821

 

The Clinically Relevant Insights Blog, part of ShawnWilsonPhD.com, shares news and research regarding psychology and wellness.

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