Cannabinoid Treatment for Stress, Anxiety and Depression

Increasing evidence suggests an important role for the endocannabinoid system 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 hypothalamic-pituitary-adrenal (HPA) axis, increased anxiety, suppressed feeding behaviour, reduced responsiveness to rewarding stimuli, hypervigilance and arousal, enhanced grooming behaviour and impaired cognitive flexibility [2] - [3].

Evidence from pre-clinical and clinical studies suggests that THC exhibits biphasic effects on mood, with low doses of THC having anxiolytic and mood-elevating effects and high doses of THC having anxiogenic and mood-lowering effects [4]Limited evidence from a small number of clinical 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, multiple sclerosis, and chronic neuropathic pain) [5] - [6].

Limited evidence from some observational studies also suggests 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 [7].

The use of THC-predominant cannabis or prescription cannabinoid medications containing primarily THC (dronabinol) to treat primary anxiety or depression should be viewed with caution, and especially discouraged in patients with a history of psychotic disorders.

References

[1] Hillard CJ. Stress regulates endocannabinoid-CB1 receptor signaling. Semin Immunol 2014 Oct;26(5):380-8.

[2] Morena M, Patel S, Bains JS, Hill MN. Neurobiological interactions between stress and the endocannabinoid system. Neuropsychopharmacology 2016 Jan;41(1):80-102.

[3] Hill MN, Patel S. Translational evidence for the involvement of the endocannabinoid system in stress-related psychiatric illnesses. Biol Mood Anxiety Disord 2013 Oct 22;3(1):19,5380-3-19.

[4] Rubino T, Zamberletti E, Parolaro D. Endocannabinoids and mental disorders. Handb Exp Pharmacol 2015;231:261-83.

[5] Crippa JA, Zuardi AW, Martin-Santos R, Bhattacharyya S, Atakan Z, McGuire P, Fusar-Poli P. Cannabis and anxiety: A critical review of the evidence. Hum.Psychopharmacol. 2009 10;24(1099-1077; 0885-6222; 7):515-23.

[6] Denson TF, Earleywine M. Decreased depression in marijuana users. Addict Behav 2006 04;31(0306-4603; 0306-4603; 4):738-42.

[7] Lev-Ran S, Roerecke M, Le Foll B, George TP, McKenzie K, Rehm J. The association between cannabis use and depression: A systematic review and meta-analysis of longitudinal studies. Psychol Med 2014 Mar;44(4):797-810