CBD against depression

Cannabidiol (CBD) shows promising potential in preclinical studies and initial clinical observations for supporting the treatment of depression—particularly mild to moderate forms and comorbid anxiety disorders. Its mechanisms of action include indirect activation of 5-HT1A receptors, modulation of the endocannabinoid system, inhibition of neuroinflammatory processes, and promotion of neuroplasticity. Animal models demonstrate antidepressant effects comparable to those of conventional antidepressants. Initial human studies and case reports suggest mood-enhancing, anxiolytic, and stress-reducing effects—especially with regular intake of moderate doses (≥150 mg/day). CBD is non-sedating and has no potential for addiction. Differences from conventional antidepressants lie in its mechanism of action, side effect profile, and speed of onset. While large placebo-controlled studies are still lacking, CBD is considered a well-tolerated adjunct to existing therapies, particularly within the framework of a comprehensive psychotherapeutic approach. Medical supervision remains essential – especially in cases of concurrent psychopharmacotherapy or severe depressive symptoms.
Philip Schmiedhofer, MSc

Autor

Philip Schmiedhofer, MSc

Inhaltsverzeichnis

Can CBD help with depression?

Yes, cannabidiol (CBD) can potentially have a supportive effect on depression – especially in mild to moderate forms as well as in comorbid anxiety disorders.

How does CBD affect the serotonin level in the brain?

Cannabidiol (CBD) acts in the brain, among other things, by modulating the serotonergic system – a central network for mood, anxiety, sleep, and emotions.

What differences are there between CBD and antidepressants?

The differences between cannabidiol (CBD) and classical antidepressants lie in the mechanism of action, onset of effect, side effect profile, and range of applications.

Which studies investigate CBD for depressive moods?

CBD offers a gentler, multimodal approach, primarily acting as an anxiety reliever.

How do you properly dose CBD for depression?

The correct dosage of cannabidiol (CBD) for depression has not yet been standardized and depends on several factors, including the severity of symptoms, comorbidities, body weight, CBD formulation, and individual response.

Can CBD be used alongside psychotherapy?

Yes, cannabidiol (CBD) can be used alongside psychotherapy – especially for depression that is accompanied by anxiety disorders, sleep problems, or emotional overexcitability.

What experiences are there with CBD against depressive symptoms?

Experiences with cannabidiol (CBD) for alleviating depressive symptoms have so far been predominantly positive.

Is CBD also useful for seasonal depression?

Yes, CBD can also have a supportive effect on seasonal depression (SAD) – especially through its mood-enhancing, stress-regulating, and anxiety-reducing effects.

Are there risks or side effects with depression and CBD?

Yes, the use of cannabidiol (CBD) for depression is generally considered well-tolerated, yet there are some risks and side effects to be aware of.

How do CBD and THC differ in relation to depression?

Cannabidiol (CBD) and Tetrahydrocannabinol (THC) are two main active ingredients of the cannabis plant.

Can CBD help with depression?

Yes, cannabidiol (CBD) can potentially support depression – especially in mild to moderate forms as well as in comorbid anxiety disorders. The current body of research includes both animal experimental models and initial clinical investigations that suggest an antidepressant effect of CBD. The mechanisms of action are complex and mainly include modulation of the endocannabinoid system, an increase in serotonergic pathways (including via 5-HT1A receptors), inhibition of inflammatory processes in the CNS, and promotion of neuroplasticity.

CBD Depression

In preclinical studies, CBD was able to significantly reduce depressive behavior in animal models, such as in the Forced Swim Test or the Tail Suspension Test. Clinical evidence comes, among others, from case series and open studies (e.g., Zuardi et al., 2017; Elms et al., 2019), in which mood improvement, better stress resilience, and reduced anxiety symptoms were reported. However, a randomized, placebo-controlled study is still pending to validly prove the antidepressant effect.

Conclusion: CBD is not an approved antidepressant but shows promising effects in preclinical models and initial human studies. Therapeutic use should always be medically supervised, especially in cases of existing psychopharmacotherapy.

How does CBD affect the serotonin level in the brain?

Cannabidiol (CBD) acts in the brain, among other things, by modulating the serotonergic system – a central network for mood, anxiety, sleep, and emotions. Unlike classic antidepressants, which primarily inhibit the reuptake of serotonin (e.g., SSRIs), CBD interacts indirectly with 5-HT1A receptors, a subtype of serotonin receptors, which is particularly strongly associated with anxiolytic and antidepressant effects.

Target structure

Effect of CBD

Significance for serotonin & mood

5-HT1A receptors

Partial agonist

Enhanced serotonergic signaling, anxiolytic and antidepressant

Indirect FAAH inhibition

Increases anandamide (endogenous cannabinoid)

Anandamide modulates, among other things, serotonergic activity

stress reduction

Inhibition of cortisol and stress systems

Indirectly stabilizing serotonergic balance

Neuroinflammation

Inhibition of proinflammatory cytokines (e.g., IL-6, TNF-α)

Inflammation disrupts serotonin balance – CBD can counteract

  • Preclinical studies show that CBD in the Forced Swim Test (FST) – an animal model for depressive symptoms – acts similarly to imipramine (a tricyclic antidepressant), especially through activation of 5-HT1A receptors.
  • Neuroimaging studies in humans (e.g., Crippa et al., 2011) show altered activity in limbic regions after CBD administration, which is indirectly related to serotonergic effects.
  • CBD affects not directly the serotonin level in terms of an increase in concentration in the synaptic cleft, but rather alters the sensitivity and signal transmission at certain serotonin receptors.

CBD acts antidepressively, not by increasing serotonin levels, but through Modulation of serotonergic receptors, in particular 5-HT1A. This indirect effect explains its anxiolytic and potentially mood-enhancing properties – without classic side effects like those of SSRIs. The effects are dose-dependent, individually variable, and often stabilize only after several days of administration.

CBD antidepressants

What differences are there between CBD and antidepressants?

The differences between Cannabidiol (CBD) and classical antidepressants lie in mechanism of action, onset of effect, side effect profile, and spectrum of use. While antidepressants like SSRIs or tricyclic antidepressants directly interfere with serotonin balance, CBD acts indirectly, especially via 5-HT1A receptors, which endocannabinoid system and anti-inflammatory signaling pathways.

Criterion

CBD

Antidepressants (SSRI, SNRI, TCA)

Mechanism of Action

Indirect modulation of 5-HT1A, FAAH, ECS

Direct inhibition of serotonin/norepinephrine reuptake

Onset of effect

Sometimes fast (within a few days for anxiety), delayed in depression

Usually 2–4 weeks

Main area of application

Anxiety, stress, sleep disorders; adjunctive in depression

Depression, anxiety disorders, obsessive-compulsive disorders

Side effects

Mild: fatigue, nausea, rarely elevated liver enzymes

Common: nausea, loss of libido, weight gain, sleep disturbance

Addiction potential

No known addiction potential

No addiction potential, but withdrawal symptoms possible

Effect on sleep

Supportive (especially in stress-related insomnia)

Can disturb or improve sleep – varies individually

Long-term data

Limited (especially present in epilepsy)

Extensively clinically documented

Availability / approval

No approved medication for depression

Prescription drugs with clinical approval

Effect profile

Multimodal: anxiolytic, stress-reducing, neuroprotective

Primarily mood-enhancing, via monoaminergic systems

  • CBD is not an approved alternative to antidepressants, but can be used for mild to moderate depressive moods – especially anxiety-related depression or sleep problems – act supportively.
  • antidepressants are standardized, well-studied medications with defined indications, but often with side effects and long latency periods.
  • CBD offers a gentler, multimodal approach, acting primarily anxiolytic, stress-regulating, and anti-inflammatory, but is not sufficiently proven for severe depressive episodes.

If you want, I can also formulate a brief recommendation for therapeutic use (e.g., as an add-on) or create a graphical comparison table for a professional audience.

Which studies investigate CBD for depressive moods?

Author(s), Year

Title

Gniewko Wieckiewicz et al., 2022

Cannabidiol (CBD) in the Self-Treatment of Depression—Exploratory Study and a New Phenomenon of Concern for Psychiatrists

María S. García-Gutiérrez et al., 2020

Cannabidiol: A Potential New Alternative for the Treatment of Anxiety, Depression, and Psychotic Disorders

Thersilla Oberbarnscheidt et al., 2020

The Impact of Cannabidiol on Psychiatric and Medical Conditions

Jozsef Haller, 2024

Herbal Cannabis and Depression: A Review of Findings Published over the Last Three Years

Rabia Khan et al., 2020

The therapeutic role of Cannabidiol in mental health: a systematic review

How do you properly dose CBD for depression?

The correct Dosage of Cannabidiol (CBD) in depression is not yet standardized and depends on several factors, including severity of symptoms, comorbidities, Body weight, CBD formulation and individual response. The study situation suggests that low doses are often insufficient, while medium to high doses (from approx. 150 mg/day) in human studies anxiolytic and mood-enhancing effects can be shown. CBD can support depressive symptoms, especially when Anxiety, sleep problems or chronic stress are involved. The effective dosage is usually significantly higher than that of over-the-counter products. A concomitant medical consultation is recommended, especially when taken simultaneously with other psychotropic drugs.

CBD Depression Therapy

Can CBD be used alongside psychotherapy?

Yes, Cannabidiol (CBD) can be used adjunctively with psychotherapy used – especially in depression associated with Anxiety disorders, sleep problems or emotional overexcitability occur together. Available studies suggest that CBD can improve psychophysiological conditions, which facilitate successful psychotherapeutic work.

Mechanism of Action

Relevance for psychotherapy

Anxiolytic effect (via 5-HT1A receptors)

Reduction of social inhibition, panic, internal tension before or during sessions

Stress modulation / cortisol reduction

Beneficial in chronic overload and maladaptive stress reactions

Sleep regulation

Improvement of regeneration and cognitive processing

Promotion of emotional regulation

Stabilization in dysphoric mood, irritability, or impulsivity

Improvement of memory consolidation (theoretically via CB1/Anandamide)

Can support positive learning effects from therapy (e.g., in exposure therapy)

CBD can be a meaningful complement to psychotherapy represent – especially in affective dysregulation, anxiety and stress-associated complaints. It indirectly supports therapeutic work by emotional and physiological burdens reduced. Important in this context is a individual and controlled use as well as a clearly defined therapeutic context.

What experiences are there with CBD against depressive symptoms?

Experiences with cannabidiol (CBD) for alleviating depressive symptoms have so far been predominantly positive, although the evidence base heterogeneous and is still in development. Both in clinical studies, case reports as well as in patient observations many affected individuals report a noticeable improvement in mood, one Decrease in inner restlessness, better sleep and a increased stress resilience.

Clinical and preclinical experiences:

  • Case series and small human studies (e.g., Elms et al., 2019; Zuardi et al., 2017) show a Reduction of depressive symptoms especially with comorbid anxiety disorders or sleep disturbances.
  • In animal models typical symptoms could be reduced by CBD administration Behavioral characteristics of depressive episodes such as lack of drive, social withdrawal, or hopelessness – among others, by influencing the serotonergic system, the HPA axis, and neuroinflammatory processes (Sales et al., 2019; Linge et al., 2016).
  • In the Study by Elms et al. (2019) patients with PTSD who received CBD in addition to therapy showed a significant reduction in anxiety and depression scores (measured using standardized scales).
  • Long-term observations suggest that CBD – with regular use – can Mood stabilization contribute and thus also mitigate recurrent depressive episodes can.

Subjective user experiences:

  • Many users report in non-scientific forums that they feel less down, emotionally more stable and calmer inside feel.
  • Particularly emphasized is often the reduction of rumination, tension and emotional exhaustion.
  • At the same time, experience reports also show that low dosages (<50 mg/day) frequently not sufficiently effective are, while medium to higher dosages (150–300 mg/day) are described as more effective.

Limitations:

  • The previous state of research is often based on open designs, small samples or preclinical data.
  • There are so far no approved CBD therapy for depression, so the use should always be considered as Off-label to be understood.

Conclusion:

CBD is regarded by many affected by depression as supportive and stabilizing experienced – especially in combination with other therapeutic measures such as psychotherapy. Particularly in comorbid anxiety disorders, sleep problems, and stress burden CBD appears to be effective. A medically supervised application with individual dose adjustment is recommended.

Is CBD also useful for seasonal depression?

Yes, CBD can also support seasonal depression (SAD) – especially through its mood-enhancing, stress-regulating, and anxiolytic effects. Studies suggest that CBD through the modulation of the serotonergic system (e.g., 5-HT1A receptors) as well as a reduction of neuroinflammatory processes can indirectly alleviate depressive symptoms that typically increase during seasons with little light. Although specific studies on SAD are still lacking, use within the framework of a holistic therapy concept (including light therapy, exercise, and sleep hygiene) well justified.

Are there risks or side effects with depression and CBD?

Yes, the use of cannabidiol (CBD) in depression is generally considered well tolerated, yet some Risks and side effects to be noted – especially at higher dosages or when taken with other medications simultaneously.

Side effect

Frequency

Remark

Fatigue / sedation

frequent (especially at >100 mg/day)

May occur with daily dosing, possibly helpful in the evening

Appetite change

occasional

Both increase and decrease possible

Nausea / stomach discomfort

rare

Dose-dependent, mostly with rapid titration

Mild dizziness

rare

Especially in cases of low blood pressure

Interactions with SSRI / SNRI

potentially relevant

CBD inhibits CYP450 enzymes (especially CYP2C19, CYP3A4) → altered plasma levels possible

Special risks

  • Psychiatric comorbidities: In cases of severe depression with suicide risk, CBD should not be considered a substitute for guideline-based therapy.
  • Drug interactions: When taking antidepressants, neuroleptics, or mood stabilizers simultaneously, medical supervision is required.
  • Lack of standardization: Over-the-counter CBD products vary greatly in quality, purity, and dosage.

CBD is generally well tolerated in depression and can play a supportive role – but never without medical consultation and supervision, especially with existing medication or severe symptoms. Slow dose escalation and careful monitoring are essential.

CBD depression symptoms

How do CBD and THC differ in relation to depression?

Cannabidiol (CBD) and Tetrahydrocannabinol (THC) are two main active compounds of the cannabis plant, which differ in their Mode of action, psychotropic effects, and their therapeutic potential in depression fundamentally differ:

Aspect

CBD (Cannabidiol)

THC (Tetrahydrocannabinol)

Psychotropic

No

Yes (intoxicating, psychoactive)

Effect on mood

Anxiolytic, antidepressant effect via 5-HT1A, CB2 etc.

Short-term mood-enhancing, long-term partly dysphoric

Receptor effect

Indirect modulation of 5-HT1A, GPR55, CB2

Agonist at CB1 receptors (centrally active)

Risk of dependency

Very low

Increased with regular or high dosing

Effect on sleep

Sleep-regulating, anxiolytic (dose-dependent)

Sedating, can suppress REM sleep

Long-term effect

Potentially stabilizing

Risk of affective disorders with high/longer use

State of research on depression

Increasingly positive (preclinical and initial clinical data)

Inconsistent, high risk of depression with chronic use

CBD shows mood-stabilizing and antidepressant effects, without the risk of psychotropic side effects or addiction. It acts through non-psychoactive pathways, including the serotonergic system. THC, on the other hand, can short-term mood-enhancing, but in the long term depression-promoting act – especially with regular use or genetic predisposition. From a psychiatric perspective, CBD clearly preferred over THC in the supportive treatment of depressive symptoms.

Sources

Wieckiewicz, G., Stokłosa, I., Stokłosa, M., Gorczyca, P., & Pudlo, R. (2022). Cannabidiol (CBD) in the Self-Treatment of Depression-Exploratory Study and a New Phenomenon of Concern for Psychiatrists. Frontiers in psychiatry, 13, 837946. https://doi.org/10.3389/fpsyt.2022.837946

García-Gutiérrez, M. S., Navarrete, F., Gasparyan, A., Austrich-Olivares, A., Sala, F., & Manzanares, J. (2020). Cannabidiol: A Potential New Alternative for the Treatment of Anxiety, Depression, and Psychotic Disorders. Biomolecules, 10(11), 1575. https://doi.org/10.3390/biom10111575

Oberbarnscheidt, T., & Miller, N. S. (2020). The Impact of Cannabidiol on Psychiatric and Medical Conditions. Journal of clinical medicine research, 12(7), 393–403. https://doi.org/10.14740/jocmr4159

Haller J. (2024). Herbal Cannabis and Depression: A Review of Findings Published over the Last Three Years. Pharmaceuticals (Basel, Switzerland), 17(6), 689. https://doi.org/10.3390/ph17060689

Khan, R., Naveed, S., Mian, N., Fida, A., Raafey, M. A., & Aedma, K. K. (2020). The therapeutic role of Cannabidiol in mental health: a systematic review. Journal of cannabis research, 2(1), 2. https://doi.org/10.1186/s42238-019-0012-y

Zuardi, A. W., Crippa, J. A., Hallak, J. E., Moreira, F. A., & Guimarães, F. S. (2006). Cannabidiol, a Cannabis sativa constituent, as an antipsychotic drug. Brazilian journal of medical and biological research = Revista brasileira de pesquisas medicas e biologica, 39(4), 421–429. https://doi.org/10.1590/s0100-879x2006000400001

Elms, L., Shannon, S., Hughes, S., & Lewis, N. (2019). Cannabidiol in the Treatment of Post-Traumatic Stress Disorder: A Case Series. Journal of alternative and complementary medicine (New York, N.Y.), 25(4), 392–397. https://doi.org/10.1089/acm.2018.0437

Crippa, J. A., Derenusson, G. N., Ferrari, T. B., Wichert-Ana, L., Duran, F. L., Martin-Santos, R., Simões, M. V., Bhattacharyya, S., Fusar-Poli, P., Atakan, Z., Santos Filho, A., Freitas-Ferrari, M. C., McGuire, P. K., Zuardi, A. W., Busatto, G. F., & Hallak, J. E. (2011). Neural basis of anxiolytic effects of cannabidiol (CBD) in generalized social anxiety disorder: a preliminary report. Journal of psychopharmacology (Oxford, England), 25(1), 121–130. https://doi.org/10.1177/0269881110379283

Sales, A. J., Fogaça, M. V., Sartim, A. G., Pereira, V. S., Wegener, G., Guimarães, F. S., & Joca, S. R. L. (2019). Cannabidiol Induces Rapid and Sustained Antidepressant-Like Effects Through Increased BDNF Signaling and Synaptogenesis in the Prefrontal Cortex. Molecular neurobiology, 56(2), 1070–1081. https://doi.org/10.1007/s12035-018-1143-4

Linge, R., Jiménez-Sánchez, L., Campa, L., Pilar-Cuéllar, F., Vidal, R., Pazos, A., Adell, A., & Díaz, Á. (2016). Cannabidiol induces rapid-acting antidepressant-like effects and enhances cortical 5-HT/glutamate neurotransmission: role of 5-HT1A receptors. Neuropharmacology, 103, 16–26. https://doi.org/10.1016/j.neuropharm.2015.12.017

Philip Schmiedhofer, MSc

Philip Schmiedhofer, MSc

Philip is managing director and co-founder of cannhelp GmbH. With studies in medical engineering and molecular biology, specialized in brain science and focusing on cannabinoids, he is recognized as an expert in the use of cannabinoids in medicine. As a medical device consultant, he also leads the sales of cannmedic and offers specialized advice for medical professionals. His expertise includes the development and sales of cannabinoid-based products. In the field of research, he participates in significant basic research at the Centre for Brain Research of the Medical University of Vienna. As co-founder and current managing director of cannmedic GmbH, a pioneer in the trade of CBD medical devices, he has many years of entrepreneurial experience. Furthermore, he maintains an extensive network in the field and advises internationally operating companies in the area of medical cannabinoids.