Depression – Medical Marijuana Research Overview

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Depression is a serious mood disorder that affects about 6.7% of adults and 3.3% of 13 to 18 year olds in the U.S. Studies have shown cannabis has antidepressant and antipsychotic effects.

Overview of Depression

Depression is a mood disorder that causes emotional problems and a persistent feeling of sadness and disinterest. Depressive illnesses are disorders of the brain and are caused by a combination of genetic, biological, environmental and psychological factors.

There are several forms of depression. Major depression is associated with severe symptoms that affect the ability to function in daily life. While major depression could occur only one time in one’s life, typically people diagnosed with depression experience multiple episodes throughout their lifetime. Persistent depressive disorder is when the depressed mood lasts for at least two years. Symptoms may fluctuate between being major or less severe, but they last for at least two years. Bipolar disorder, which is also called manic-depressive illness, causes a cycling of mood changes from extreme highs to extreme lows.

Some forms of depression can develop following certain experiences. Psychotic depression occurs when someone has severe depression and some form of psychosis. Postpartum depression develops in new mothers; the hormonal and physical changes they experience and the feeling of being overwhelmed causes depression. Seasonal affective disorder develops during the winter months when a person is exposed to less natural sunlight.

Depression causes feelings of sadness or hopelessness, angry outbursts, loss of interest or pleasure, sleep disturbances, lack of energy, anxiety, changes in appetite, and feelings of worthlessness.

Depression can be effectively treated with medications and psychological counseling. For some who experience severe depression, a hospital stay or day treatment programs are needed.

Findings: Effects of Cannabis on Depression

Research has found that the endocannabinoid system is associated with the management of mood. A dysfunction in the system, which causes a reduction in cannabinoid concentrations, has been found to cause mood disorders and depression (Hill & Gorzalka, 2009) (Hillard & Liu, 2014) (Gorzalka & Hill, 2011) (Smaga, et al., 2014). This dysfunction is likely caused by chronic stress, as one study found that an exposure to stress significantly reduced endocannabinoid concentrations in women diagnosed with major depression (Hill, et al., 2009). These findings suggest that cannabinoids, like tetrahydrocannabinol (THC) and cannabidiol (CBD), which are found in cannabis and influence the endocannabinoid system, could assist in the regulation of the endocannabinoid system and therefore offer therapeutic potential (Ashton & Moore, 2011) (Hill, et al., 2009) (Smaga, et al., 2014).

Studies have confirmed that both THC and CBD’s impact on the endocannabinoid system have sedative, antidepressant and antipsychotic effects (Ashton, Moore, Gallagher & Young, 2005) (El-Alfy, et al, 2010) (Walsh, et al. 2016). An animal trial found that the administration of cannabinoids was able to restore normal endocannabinoid function, which in turn stabilized mood and eased depression (Haj-Dahmane & Shen, 2014).

Numerous animal studies have demonstrated CBD’s anti-anxiety and antidepressant effects (de Mello Schier, et al., 2014) (Zanelati, et al., 2010) (El-Alfy, et al, 2010). In a human study, CBD administration before or after individuals were conditioned to a colored box with electric shocks caused a reduction in automatic contextual responding, suggesting that CBD could be effective in treating anxiety disorders (Das, et al., 2013). Most recently, CBD was found in an animal trial to have rapid antidepressant and antianxiety effects (Linge, et al., 2016). Evidence indicates that its CBD’s interaction with the 5-HT1A neuro-receptor that creates these effects (de Mello Schier, et al., 2014) (Zanelati, et al., 2010).

THC has been found to alter the response to negative images or emotions. In one study, people with THC in their bloodstream experienced a reduction in negative bias in emotional processing (Boxxing, et al., 2013). A human study found that both THC and CBD were effective at reducing the response to fearful faces (Fusar-Poli, et al., 2009).

Cannabis could also assist in managing the health risks associated with depression. Depression has been linked to a higher risk of cardiovascular disease and a higher resting systolic blood pressure. However, one study found that the administering of cannabinoids in women diagnosed with depression was effective at regulating their high blood pressure (Ho, et al., 2012).

It’s important to note that marijuana use has previously been associated with a greater risk of depressive symptoms (Bricker, et al., 2007). However, a survey found that adults that regularly use marijuana are not at a greater risk of depression than non-using adults (Denson & Earleywine, 2006). In addition, a 2012 study found that suicide rates decreased by an overall of 5% in states with medical marijuana approximately after legislation was adopted. Changes in marijuana laws caused an 11 percent decrease in the suicide rate of 20 through 29-year-old males and a 9% decrease in the suicide rate of 30 to 39-year-old males, with a sharp decrease shown in 15 to 19-year old males (Anderson, Rees & Sabia, 2012).

States That Have Approved Medical Marijuana for Depression

No states have approved medical marijuana specifically for the treatment of depression. However, in Washington D.C., any condition can be approved for medical marijuana as long as a DC-licensed physician recommends the treatment. In addition, a number of other states will consider allowing medical marijuana to be used for the treatment of depression with the recommendation from a physician. These states include: California (any debilitating illness where the medical use of marijuana has been recommended by a physician), Connecticut (other medical conditions may be approved by the Department of Consumer Protection), Massachusetts (other conditions as determined in writing by a qualifying patient’s physician), Nevada (other conditions subject to approval), Oregon (other conditions subject to approval), Rhode Island (other conditions subject to approval), and Washington (any “terminal or debilitating condition”).

Recent Studies on Cannabis’ Effect on Depression
  • Numerous animal studies have shown CBD to have antidepressant effects.
    Antidepressant-like and anxiolytic-like effects of cannabidiol: a chemical compound of Cannabis sativa.
  • CBD was found to provide antidepressant effects comparable to the antidepressant drug imipramine.
    Antidepressant-like effects of cannabidiol in mice: possible involvement of 5-HT1A receptors.

Anderson, D.M., Rees, D.I., and Sabia, J.J. (2012, January 7). High on Life? Medical Marijuana Laws and Suicide. Cato Institute, 17. Retrieved from

Ashton, C.H., and Moore, P.B. (2011, October). Endocannabinoid system dysfunction in mood and related disorders. Acta Psychiatrica Scandinavica, 124(4), 250-61.

Ashton, C.H., Moore, P.B., Gallagher, P., and Young, A.H. (2005). Cannabinoids in bipolar affective disorder: a review and discussion of their therapeutic potential. Journal of Psychopharmacology, 19(3), 293-300.

Bossing, M.G., van Hell, H.H., Jager, G., Kahn, R.S., Ramsey, N.F., and Jansma, J.M. (2013, December). The endocannabinoid system and emotional processing: a pharmacological fMRI study with ∆9-tetrahydrocannabinol. European Neuropsychopharmacology, 23(12), 1687-97.

Bricker, J.B., Russo, J., Stein, M.B., Sherbourne, C., Craske, M., Schraufnagel, T.J., and Roy-Byrne, P. (2007). Does occasional cannabis use impact anxiety and depression treatment outcomes?: Results from a randomized effectiveness trial. Depression and Anxiety, 24(6), 392-8.

Das, R.K., Kamboj, S.K., Ramadas, M., Yogan, K., Gupta, V., Redman, E., Curran, H.V., and Morgan, C.J. (2013, April). Cannabidiol enhances consolidation of explicit fear extinction in humans. Psychopharmacology, 226(4), 781092.

de Mello Schier, A.R., de Oliveira Ribeiro, N.P., Coutinho, D.S., Machado, S., Arias-Carrion, O., Crippa, J.A., Zuardi, A.W., Nardi, A.E., and Silva, A.C. (2014). Antidepressant-like and anxiolytic-like effects of cannabidiol: a chemical compound of Cannabis sativa. CNS & Neurological Disorders Drug Targets, 13(6), 953-60.

Denson, T.F., and Earleywine, M. (2006, April). Decreased depression in marijuana users. Addictive Behaviors, 31(4), 738-742.

Depression (major depressive disorder). (2015, July 22). Mayo Clinic. Retrieved from

El-Alfy, A. T., Ivey, K., Robinson, K., Ahmed, S., Radwan, M., Slade, D., … Ross, S. (2010). Antidepressant-like effect of Δ9-tetrahydrocannabinol and other cannabinoids isolated from Cannabis sativa L. Pharmacology, Biochemistry, and Behavior, 95(4), 434–442.

Fusar-Poli, P., Crippa, J.A., Bhattacharyya, S., Borgwardt, S.J., Allen, P., Martin-Santos, R., Seal, M., Surguladze, S.A., O’Carrol., C., Atakan, Z., Zuardi, A.W., and McGuire, P.K. (2009, January). Distinct effects of {delta}9-tetrahydrocannabinol and cannabidiol on neural activation during emotional processing. Archives of General Psychiatry, 66(1), 95-105.

Gorzalka, B.B., and Hill, M.N. (2011, August 15). Putative role of endocannabinoid signaling in the etiology of depression and actions of antidepressants. Progress in Neuro-Pschopharmacology & Biological Psychiatry, 35(7), 1575-85.

Haj-Dahmane, S., and Shen, R.Y. (2014, October 29). Chronic stress impaires α1-adrenoceptor-induced endocannabinoid-dependent synaptic plasticity in the dorsal raphe nucleus. The Journal of Neuroscience, 34(44), 14560-14570.

Hill, M.N., Gorzalka, B.B. (2009, December). The endocannabinoid system and the treatment of mood and anxiety disorders. CNS & Neurological Disorders Drug Targets, 8(6), 451-8.

Hill, M.N., Hillard, C.J., Bambico, F.R., Patel., S, Gorzalka, B.B., and Gobbi, G. (2009, September). The therapeutic potential of the endocannabinoid system for the development of a novel class of antidepressants. Trends in Pharmacological Sciences, 30(9), 484-93.

Hill, M. N., Miller, G. E., Carrier, E. J., Gorzalka, B. B., & Hillard, C. J. (2009). Circulating Endocannabinoids and N-Acyl Ethanolamines Are Differentially Regulated in Major Depression and Following Exposure to Social Stress. Psychoneuroendocrinology, 34(8), 1257–1262.

Hillard, C. J., & Liu, Q. (2014). Endocannabinoid Signaling in the Etiology and Treatment of Major Depressive Illness. Current Pharmaceutical Design, 20(23), 3795–3811.

Ho, W. V., Hill, M. N., Miller, G. E., Gorzalka, B. B., & Hillard, C. J. (2012). Serum contents of endocannabinoids are correlated with blood pressure in depressed women. Lipids in Health and Disease, 11, 32.

Linge, R., Jimenez-Sanchez, L, Campa, L., Pilar-Cuellar, F., Vidal, R., Pazos, A., Adell, A., and Diaz, A. (2016, April). Cannabidiol induces rapid-acting antidepressant-like effects and enhances cortical 5-HT/glutamate neurotransmission: role of 5-HT1A receptors. Neuropharmacology, 103, 16-26.

Smaga, I., Bystrowska, B., Gawliński, D., Pomierny, B., Stankowicz, P., & Filip, M. (2014). Antidepressants and Changes in Concentration of Endocannabinoids and N-Acylethanolamines in Rat Brain Structures. Neurotoxicity Research, 26(2), 190–206.

Walsh, Z., Gonzalez, R., Crosby, K., S Thiessmen, M., Carroll, C., and Bonn-Miller, M.O. (2016, October 12). Medical cannabis and mental health: A guided systematic review. Clinical Psychology Review, 51, 15-29.

What Is Depression? (n.d.). National Institute of Mental Health. Retrieved from

Zanelati, T., Biojone, C., Moreira, F., Guimarães, F., & Joca, S. (2010). Antidepressant-like effects of cannabidiol in mice: possible involvement of 5-HT1A receptors. British Journal of Pharmacology, 159(1), 122–128.

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