Does Cannabis Treat or Trigger Anxiety ?

The unique contributions of cannabinoids and terpenes

According to a survey of 1,429 medical cannabis patients in Washington state, 58.1% of responders indicated that they use cannabis for anxiety; this was topped only for medical use for pain (61.2%). [1] A large body of preclinical and some clinical data indicate that cannabis can effectively reduce symptoms of anxiety; however, cannabis consumption can cause paranoia and increase anxiety. [2,3] These effects, while paradoxical in nature, can be explained by the chemical composition of the cannabis plant.

Consuming the cannabis plant in its intact form subjects the user to hundreds of different phytochemicals. These compounds bind to a variety of receptors in the central nervous system, including the cannabinoid (CB) receptors 1 and 2, as well as transient receptor potential (TRP), GPR55, and serotonin receptors. [4]

The effects of cannabinoids and terpenes depend on a variety of factors, including compound (CBD vs. CBG), receptor (TRP vs. CB1) type, and dose. Additionally, product bioavailability, consumption method, and formulation (pure CBD vs. CBD:THC) greatly affect time course and physiological/behavioral response.[4]

THC, the “psychoactive” cannabinoid, has consistently been linked with the anxiogenic properties of cannabis. Preclinical evidence has indicated that THC exerts its effects in a dose-dependent manner, acting as an anxiolytic at low doses and as an angiogenic at high doses. [5] These effects, which have been confirmed in some human studies, appear to be mediated by the CB1 receptor. [6]

Evidence from both preclinical and human studies have indicated that CBD maybe an effective anxiolytic treatment. These effects, which are mediated by serotonin receptors, appear to be optimal when CBD is taken orally at dosesranging from 300 to 600 mg. [7] However, there is some evidence that these effects might be similarly dose-dependent, as is the case with THC.Though several other cannabinoids also have beneficial effects on anxiety, there is limited data available.

Some terpenespossess anxiolytic properties as well. [5] One such terpene, linalool, may affect anxiety by reducing release of glutamate, an excitatory neurotransmitter; linalool is the active component of lavender, which is commonly used to alleviate stress and promote calm. [8] In addition, animals treated with β-Caryophyllene, a CB2 receptor agonist, and nerolidol displayed a reduction in anxiety-like behaviors. [9-10]

There is considerable evidence that certain compounds within the cannabis plant can effectively reduce anxiety. Any potential dose-dependent effects can be mitigated at home through careful trial and error.

References

1. Sexton, M., Cuttler, C., Finnell, J.S., Mischley, L.K., “A Cross-Sectional Survey of Medical Cannabis Users: Patterns of Use and Perceived Efficacy”, Cannabis Cannabinoid Res, 2016, Volume 1, pg. 131-138. (impact factor: N/A; cited by: 39)

2. Zhang, M.W., Ho, R.C., “The Cannabis Dilemma: A Review of Its Associated Risks and Clinical Efficacy”, Journal of Addiction, 2015, Volume 2015, pg.1-6. (impact factor: 2.406; cited by: 27)

3. Hall, W., Solowij, N., “Adverse Effects of Cannabis”, The Lancet, 1998, Volume 352, pg. 1611-1616. (impact factor: 53.254; cited by: 943)

4. Izzo, A.A., Borrelli, F., Capasso, R., Di Marzo, V., Mechoulam, R., “Non-psychotropic Plant Cannabinoids: New Therapeutic Opportunities from an Ancient Herb”, Trends Pharmacol Sci, 2009,Volume 30, pg. 515-527. (impact factor: 10.148; cited by: 517)

5. Kamal, B.S.,Kamal, F., Lantela, D.E., “Cannabis and the Anxiety of Fragmentation—A Systems Approach for Finding an Anxiolytic Cannabis Chemotype”, Front Neurosci, 2018, Volume 12, pg. 1-14. (impact factor: 3.877; cited by: N/A)

6. Bhattacharyya, S., Egerton, A., Kim, E., et al., “Acute Induction of Anxiety in Humans by Delta-9-tetrahydrocannabinol Related to Amygdalar Cannabinoid-1 (CB1) Receptors”, Sci Rep, 2017, Volume 7, pg.1-5 (impact factor: 4.122; cited by: 13)

7. Blessing, E.M., Steenkamp, M.M., Manzanares, J., Marmar, C.R., “Cannabidiol as a Potential Treatment for Anxiety Disorders”, Neurotherapeutics, 2015, Volume 12,
   pg. 825-836.(impact factor: 5.719; cited by: 126)

8. Silva Brum, L.F., Emanuelli, T., Souza, D.O., Elisabetsky, E., “Effects of Linalool on Glutamate Release and Uptake in Mouse Cortical Synaptosomes”, Neurochem Res, 2001, Volume 26, pg. 191-194. (impact factor: 2.772; cited by: 104)

9. Bahi, A., Al Mansouri, S., Al Memari, E., Al Ameri, M., Nurulain, S.M., Ojha, S.,
   “β-Caryophyllene, a CB2 Receptor Agonist Produces Multiple Behavioral Changes Relevant to Anxiety and Depression in Mice”, Physiol Behav, 2014,Volume 135,
   pg. 119-124. (impact factor: 3.033; cited by: 97)

10. Goel, R.K., Kaur D., Pahwa, P., “Assessment of Anxiolytic Effect of Nerolidol in Mice”, Indian J Pharmacol, 2016, Volume 48, pg. 450-452. (impact factor: 0.902; cited by: 4)