Is Tetrahydrocannabinol (THC) associated with depression?

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From the Guidelines

THC use is associated with a higher risk of developing depression, particularly in adolescents and young adults, as well as older adults, as evidenced by recent studies 1. The relationship between THC and depression is complex, and the effects can vary widely based on individual factors, including genetics, existing mental health conditions, frequency of use, and dosage. Some key points to consider include:

  • Cannabis use in early youth is associated with conditions that include neuropsychological and neurodevelopmental decline, elevated risk for psychotic disorders in adulthood, higher risk for later depression, and suicidal ideation or behavior 1.
  • Limited available evidence suggests that older adults who use cannabis may be at higher risk for behavioral health issues, including anxiety and depression 1.
  • People who initiate cannabis use at a young age may have an elevated risk for developing use disorder, which can also contribute to depression 1. The effects of THC on the brain's endocannabinoid system, which regulates mood, stress response, and other functions, can disrupt normal neurotransmitter activity, potentially leading to chemical imbalances associated with depression. If you're concerned about depression, it's advisable to speak with a healthcare provider before using cannabis products, especially if you have a personal or family history of mental health conditions. Key considerations for healthcare providers include:
  • Assessing the individual's risk factors for depression and other mental health conditions before recommending cannabis use.
  • Monitoring patients for signs of depression or other mental health issues if they are using cannabis products.
  • Providing education on the potential risks and benefits of cannabis use, particularly in vulnerable populations such as adolescents and older adults.

From the Research

THC and Depression

  • There is a growing body of evidence pointing to the co-occurrence of cannabis use and depression 2.
  • Some evidence suggests that the use of cannabis may lead to the onset of depression, but strong evidence points to the inverse association, i.e., that depression may lead to the onset or increase in cannabis use frequency 2.
  • Observational and epidemiological studies have not indicated a positive long-term effect of cannabis use on the course and outcome of depression 2.

Association Between Cannabis Use and Depression

  • The association between cannabis use and depression may be stronger among men during adolescence and emerging adulthood and stronger in women during midlife 2.
  • There is an indication for potential genetic correlation contributing to the comorbidity of cannabis dependence and major depression, namely that serotonin (5-HT) may mediate such association 2.
  • Preclinical evidence suggests that alteration in the endocannabinoid system could potentially benefit patients suffering from depression, but the issue of using cannabis as an anti-depressant is at an early stage of examination and there is little evidence to support it 2.

Selective Serotonin Reuptake Inhibitors (SSRIs) and Depression

  • SSRIs are a class of drugs that alter the functioning of the serotonin system by the potentiation of serotonin through the negative allosteric modulation of its neuronal uptake by the human serotonin transporter 3.
  • SSRIs show few side effects compared to those caused by traditional antidepressants and they vary in the binding interactions formed during binding 3.
  • The combination of an SSRI and cognitive behavioral therapy (CBT) consistently produces greater improvement than either treatment alone in youth with depression and anxiety 4.

Limitations of Current Research

  • There is a lack of understanding of the complexities and interactions between SSRIs in the developing brain of a young person with depression 5.
  • More research is needed to understand the effect of SSRIs on cognitive function in depressed patients and the influencing factors 6.

References

Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

Research

Cannabis and Depression.

Advances in experimental medicine and biology, 2021

Research

Selective Inhibition of the Serotonin Transporter in the Treatment of Depression: Sertraline, Fluoxetine and Citalopram.

Neuropsychopharmacologia Hungarica : a Magyar Pszichofarmakologiai Egyesulet lapja = official journal of the Hungarian Association of Psychopharmacology, 2020

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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