The Endocannabinoid System, Cannabinoids and Anxiety

The endocannabinoid system and its role in mental health

There is increasing evidence suggesting the endocannabinoids system plays an important role in the regulation of stress, mood and psychiatric disorders.1 Pharmacological or genetic disruption of endocannabinoid signaling in animals produces a neurobehavioural response that mimics the classical stress response including activation of the HPA axis, increased anxiety, suppressed feeding behaviour, reduced responsiveness to rewarding stimuli, hypervigilance and arousal, enhanced grooming behaviour and impaired cognitive flexibility.1

In periods of acute or chronic stress, there appears to be a reduction in the endocannabinoid anandamide.1 This is thought to lead to the increase in anxiety, HPA axis activity and other symptoms of mood disorders.1

Evidence supporting the role of cannabis for anxiety

One of the most common reasons for the consumption of medical cannabis is for the reduction of anxiety or stress.2 Until recently, there was very little evidence on the potential role of cannabis in anxiety management

Health Canada’s Information for Health Care Professionals: Cannabis (marihuana, marijuana) and the cannabinoids was published in October 2018. This extensive systematic review analyzed pre-clinical and clinical data on the cannabis evidence for the management of anxiety. The anxiety findings from this systematic review are found in Table 1

Table 1 – Cannabis and Anxiety1 1
THC has a biphasic effect on mood
  • Low doses of THC are associated with an anxiolytic and mood-elevating effect

  • High doses of THC are associated with anxiety and mood-lowering effects

THC and cannabinoids improve anxiety and depression in people with chronic illnesses
  • A small number of studies of THC-containing cannabis/certain prescription cannabinoids suggests that these drugs could improve symptoms of anxiety and depression in patients suffering from anxiety and/or depression secondary to certain chronic diseases (e.g. patients with HIV/AIDS, MS, and chronic neuropathic pain).

CBD exhibits an anxiolytic benefit
  • Pre-clinical studies suggest that CBD exhibits anxiolytic effects in various animal models of anxiety

  • Clinical studies suggest CBD may have anxiolytic effects in an experimental model of social anxiety

Equal portions of THC and CBD cannabis can attenuate anxiety and depression with high THC cannabis
  • Observational studies also suggest that cannabis containing equal proportions of CBD and THC is associated with an attenuation of some perturbations in mood (anxiety/dejection) seen with THC-predominant cannabis in patients using cannabis for medical purposes

Patients use cannabis for anxiety

Patient survey data from medical cannabis users suggest that anxiety/stress is one of the most common reasons for medical cannabis use.2 These observational studies have reported significant effect on anxiety-related symptoms with a low incidence of adverse effects.2 One observational study found that approximately two-thirds of medical cannabis users were able to reduce the use of other prescription medications.3 A significant portion of these patients were able to reduce or stop medications for anxiety such as benzodiazepines and antidepressants.

  1. Health Canada. Information for Health Care Professionals: Cannabis (marihuana, marijuana) and the cannabinoids. aem. Published October 12, 2018. Accessed October 15, 2018.

  2. Morin CM, Benca R. Chronic insomnia. The Lancet. 24;379(9821):1129-1141. doi:10.1016/S0140-6736(11)60750-2

  3. Webb CW, Webb SM. Therapeutic Benefits of Cannabis: A Patient Survey. Hawaii J Med Public Health. 2014;73(4):109-111.

  4. Roth T. Comorbid insomnia: current directions and future challenges. Am J Manag Care. 2009;15 Suppl:S6-13.

  5. Lucas P, Walsh Z. Medical cannabis access, use, and substitution for prescription opioids and other substances: A survey of authorized medical cannabis patients. Int J Drug Policy. 2017;42:30-35. doi:10.1016/j.drugpo.2017.01.011