The ABC’s of THC & CBD
Produced in the form of lotions, candles, candies and oils, Cannabidiol (CBD) products have built their popular reputation as a treatment for anxiety relief. These CBD products are shown to have the ability to ease pain and induce relaxation, ultimately relieving stressful symptoms of anxiety. Some may believe that if CBD, the second most active ingredient in marijuana, is capable of bringing about anxiety relief, then marijuana as a whole substance can relieve anxiety as well. However, the presence of Tetrahydrocannabinol (THC), which is the major psychoactive ingredient in marijuana, complicates the idea that marijuana is a solely “relaxing” drug.
Cannabis is the world’s most widely-used illicit drug, with continually increasing prevalence. Despite this high prevalence, little attention has been given to the potential risk of developing mood and anxiety disorders due to regular marijuana use - especially for users later in life. A 2019 systematic review of 11 studies involving 23,317 individuals by researchers at McGill University, however, found that cannabis use during adolescence is associated with increased odds of developing anxiety in young adulthood. In addition, the risk of depression and suicidality has also been shown to increase with the usage of marijuana during adolescence. This is especially problematic, as US individuals aged 18 to 29 years who reported cannabis use roughly doubled from 2001 to 2013, from 10.5% to 21.2%. Though we’ve known the mood-elevating properties of cannabis for a long time, it may be time to delve more deeply into the long-term negative effects that cannabis can induce in terms of mental health, and especially anxiety.[1]
While marijuana may have some short-term anxiety-relieving benefits, studies have shown that a long-term use of THC at high doses will actually increase anxiety. Over the past decade, marijuana usage has significantly increased in the United States, especially since many states have legalized marijuana use in some form. Notably, the marijuana being produced has resulted in higher THC content, while the CBD content has gradually decreased. This is potentially problematic because whileas THC in its purest form can decrease anxiety at low doses, it has been shown to actually increase anxiety at high doses, and decrease anxiety at low doses. Conversely, CBD in its purest form has been shown to decrease anxiety at all doses tested.[2]
EFFECTS OF MARIJUANA INTOXICATION
Marijuana intoxication is known to have a broad range of effects, including:[3]
Euphoria
Sense of calm
Synesthesia/blending of the senses (e.g., you may be listening to music, but seeing shapes simultaneously)
Craving sweet/salty foods
Belief of arriving at a transcendent insight
Enhanced perception
Impaired shifting focus
Lack of attention
Short-term memory loss
Poor decision-making
Decreased motor activity
Lack of motivation
THE ENDOCANNABINOID SYSTEM
The endocannabinoid system in the brain is responsible for processing feelings of anxiety, fear, and stress responses. Marijuana intoxication is often associated with calmness and being content, which increases cannabinoid and oxytocin receptor activation, and increases dopamine levels. However, once the frequent and chronic user is not intoxicated, cannabis withdrawal is mediated with stress hormone release and reduced dopamine levels. It is important to note that the endocannabinoid system plays a role in anxiety, especially because endocannabinoids modulate highly interactive stress and reward networks that create balance between pain and well-being. This means that in the long-term, the positive emotional effects of marijuana intoxication may be outweighed by negative emotional effects brought about by marijuana withdrawal.[4]
Other factors associated with the risk of increased anxiety when consuming cannabis include:[5]
Genetic vulnerability
Female gender
High usage frequency
High dosage
High THC/low CBD content
History of anxiety
CANNABINOID RECEPTORS
The psychoactive effects of marijuana are related to the cannabinoid receptor CB1, while the non-psychoactive effects are related to the cannabinoid receptor CB2. THC is the main psychoactive component of marijuana, while CBD has no psychoactive effects. The CB1 receptor is strongly expressed in the brain and central nervous system (CNS). The CB2 receptor is more pertinent in peripheral immune cells and tissues. The explanation for lack of benefit derived from THC in terms of mental health could be that chronic regular use of marijuana builds a tolerance in the user. The rise in tolerance leads to the eventual downregulation of the CB1 receptor, which means some of the negative symptoms of THC that are usually felt are exacerbated even when the user is not intoxicated.[6]
The CB1 receptor is also responsible for inhibiting the release of excitatory amino acids and GABA, which regulates other transmitter releases, such as the release of acetylcholine, dopamine, histamine, serotonin and opioid peptides. Inhibitory interneurons (GABAergic) contain high levels of CB1 receptors, while excitatory terminals (glutamatergic) contain lower levels of CB1 receptors. Dopamine receptors, which play a specific important role in emotional behavior and psychiatric disorders, also contain lower levels of CB1 receptors. THC activates the CB1 receptor to induce feelings of euphoria and even heighten negative emotions, such as anxiety. On the other hand, CBD has been shown to function as a negative allosteric regulator of CB1 receptor activation, but it does not play a role as a complete antagonist.[7] This indicates that CBD plays an inhibitory role in CB1 activation, preventing the elevated emotions that THC induced through CB1 activation. However, CBD does not completely eliminate the effects of THC when both substances are present and interacting with the CB1 receptor.
CBD VS. THC AS AN ANXIETY TREATMENT
Current data suggests that CBD is associated with anxiolytic activity, with acute doses having been found to reduce or manage anxiety. Anxiolytic activity indicates that this drug can be used to treat symptoms of anxiety by blocking certain chemicals in the nervous system that may be triggered as a reaction to stress. CBD’s anxiolytic effects have been studied in various animal models of generalized anxiety disorder, social phobia, panic disorder, and post-traumatic stress disorder (PTSD) in humans. The anxiolytic effects have been established in people with generalized social anxiety disorder (SAD), and other anxiety disorders, with a heavy influence on the limbic and paralimbic areas of the brain.[8] Higher doses of CBD did not prove to have anxiogenic effects (i.e., anxiety inducing), however, higher doses of THC in clinical human studies have shown to demonstrate common effects of anxiety. This is the reason why CBD is heavily incorporated in hemp and medicinal products.[9]
Smith & Randall (2022) note that it can be more risky to administer THC-based medical marijuana treatments for anxiety disorders since the results for this treatment are more ambiguous than CBD-based treatments. This means that some may experience an increase in symptoms of anxiety with THC-dominant products, while some patients have experienced initial feelings of anxiety with use of these products.[10]
A placebo controlled, randomized study performed by researchers at Maastricht University in 2022 focused on 26 healthy recreational cannabis users to compare the effects of THC-dominant, CBD-dominant, THC/CBD-equivalent, and placebo cannabis products on anxiety. The State-Trait Anxiety Inventory (STAI) was utilized to assess the state levels of anxiety amongst these users, along with a computer-based emotional Stroop task, questionnaire, and visual analogue scale. Some of the most significant findings were that:
THC-induced anxiety based on the STAI was independent of baseline anxiety.
THC/CBD-equivalent products result in lower state anxiety levels than THC-dominant, alone.
In comparison to the placebo product, both the THC and THC/CBD products increased state level anxiety significantly.
It was also found that at low baseline states of anxiety, the CBD-dominant product was able to entirely counteract THC-induced anxiety.
However, at a high baseline state of anxiety, the CBD-dominant product was not able to counteract THC-induced anxiety.[11]
Thus, it would appear that CBD (without the presence of THC) would work best to mitigate one’s anxiety.
BAND-AID STRATEGY
It is not uncommon for people with anxiety and mood disorders to seek medical or recreational marijuana for symptom relief, and in the short-term, users may even experience the desired symptom relief. However, the long-term effects of such usage tend not to be as positive. Mammen et al. conducted a systematic review of 12 longitudinal studies on a total of 11959 patients with a range of anxiety disorders in 2018. The researchers found that for each diagnosis, frequent cannabis users had more-severe symptoms and lower rates of remission (i.e., the total disappearance of symptoms of anxiety) than less-frequent and non-users. Some of the studies even showed that there is a link between stopping marijuana usage and symptom improvement. So while individuals with anxiety disorders may use marijuana as a temporary strategy to improve acute symptoms, the results of these studies have shown this method to actually worsen symptoms in the long run. This temporary fix is what is referred to as the “Band-Aid Strategy.”[12]
If one has been using or has previously used marijuana, and is experiencing feelings of heightened anxiety, it is crucial to contact a licensed mental health professional for guidance on how to decrease anxiety symptoms and prevent possible worsening of mental health. Before beginning to take any products with THC and/or CBD, it's also important to speak with your doctor or pharmacist to address any potential health risks.
Contributed by: Ananya Udyaver
Editor: Jennifer (Ghahari) Smith, Ph.D.
References
1 Su, M., Luo, Y., & Wang, Y. (2021). The association between cannabis use and suicidal behavior: A systematic review and meta-analysis. Journal of Affective Disorders, 294, 256-263. doi:10.1016/j.jad.2021.07.083
2 Stoner, A. (2017) Effects of Marijuana on Mental Health: Anxiety Disorders. Alcohol and Drug Abuse Institute: University of Washington. https://adai.uw.edu/pubs/pdf/2017mjanxiety.pdf
3 Ibid.
4 Ibid.
5 Ibid.
6 Ibid.
7 Graczyk, M., Łukowicz, M., & Dzierzanowski, T. (2021). Prospects for the use of cannabinoids in psychiatric disorders. Frontiers. https://www.frontiersin.org/articles/10.3389/fpsyt.2021.620073/full
8 Ibid.
9 Berenbaum, H., & Connelly, J. (2020). The effect of cannabis use on mood and anxiety disorders: Clinical implications. Current Psychiatry Reports, 22(12), 78. doi:10.1007/s11920-020-01219-z
10 Smith, K. P., & Randall, C. L. (2022). Anxiety disorders and cannabis use: A review. Substance Abuse and Rehabilitation, 13, 1361-1379. doi:10.2147/sar.s326480
11 Hutten, N. R. P. W., Arkell, T. R., Vinckenbosch, F., Schepers, J., Kevin, R. C., Theunissen, E. L., Kuypers, K. P. C., McGregor, I. S., & Ramaekers, J. G. (2022). Cannabis containing equivalent concentrations of delta-9-tetrahydrocannabinol (THC) and cannabidiol (CBD) induces less state anxiety than THC-dominant cannabis. Psychopharmacology. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9584997/
12 Mammen, G., Reuda, S., Roerecke, M., Bonato, S., Rev-Lan, S., & Rehm, J. (2018). Association of cannabis with long-term clinical symptoms in anxiety and mood disorders: a systematic review of prospective studies. The Journal of Clinical Psychiatry. 79(4). https://doi.org/10.4088/JCP.17r11839