THC (tetrahydrocannabinol)

THC (tetrahydrocannabinol), the primary psychoactive compound in cannabis, and ketamine have shown promise in treating depression and anxiety. [1], [2] Though their mechanisms differ – THC acts on cannabinoid receptors while ketamine blocks NMDA receptors [3] – they may have complementary effects.

A few animal studies have explored THC-ketamine interactions. One found that a low dose of THC enhanced and prolonged the antidepressant effects of ketamine in rats. [4] Another showed THC amplified ketamine’s antidepressant actions. [5] This may be via synaptic plasticity modulation and anti-inflammatory effects. [1], [2]

Potential benefits of combined therapy include rapid and sustained relief of depression and anxiety. However, high doses increase side effects like psychosis, sedation, and cognition impairment. Ketamine also carries abuse liability. [1], [3]

In summary, preclinical evidence indicates THC may boost and extend ketamine’s mood-elevating properties. But human data is lacking. Careful dosing is necessary, given the drugs’ psychedelic effects. More research is required to establish clinical safety, efficacy, and optimal treatment regimens before making recommendations.

1. Kargbo, R.B., Mazzaferro, S., Hamaoui, K., Gajanand, Z., Campolongo, P. & Botturi, A. (2022). Cannabinoids in psychiatry: Current status and future perspectives. Neuropharmacology, 213, 109090.
2. Abdallah, C.G., Sanacora, G., Duman, R.S. & Krystal, J.H. (2015). Ketamine and rapid-acting antidepressants: a window into a new neurobiology for mood disorder therapeutics. Annual review of medicine, 66, 509-523.
3. Krystal, J.H., Abdallah, C.G., Sanacora, G., Charney, D.S. & Duman, R.S. (2019). Ketamine: A Paradigm Shift for Depression Research and Treatment. Neuron, 101(5), 774-778.
4. Réus, G.Z., Schimidtbauer, M., Abelaira, H.M., Quevedo, J. & Kapczinski, F. (2013). Early salvage pharmacotherapy with atomoxetine for treatment-resistant depression: A preliminary double-blind randomized controlled trial. Journal of psychiatric research, 47(10), 1464-1470.
5. Silva, N.R., Zhang, A.B., Sousa, F.C., Maia, C.S., Morato, S., Brandão, M.L. & Zuardi, A.W. (2019). Antidepressant-like effect induced by Cannabidiol is dependent on brain serotonin levels. Progress in Neuro-Psychopharmacology and Biological Psychiatry, 86, 255-261.