Cannabis and Depression
Depression is a serious mood disorder. There are thousands of alternative ways to treat mild to moderate forms of depression. Some, however, experience very heavy forms of depression and typical antidepressants don't seem to help.
Most cannabis users started trying cannabis when they experienced feelings of anxiety, stress, or depression. They have seamed to not only enjoy cannabis as a medicinal use, but prefer using it over any other drugs; prescribed drugs, or street drugs.
Surveys show that as many as one-third of patients who use medical cannabis primarily use it for depression. Those who use medical cannabis for anxiety, stress, or insomnia also list depression as a second reason for using it.
In a study of 364 young cannabis users, 87% said they used it to alleviate a depressed mood.
At the moment there is little clinical data showing cannabis effective use on people with severe forms of depression such as Depressed Mood (MD) or Major Depressive Disorder (MDD). With the passing of new laws, in the near future, more studies will be conducted and we can get a better idea of how cannabis effects people with various forms of depression.
Caution must be used when trying cannabis to treat depression. At the moment it is unwise to use cannabis alone to treat MDD. You must talk with a trusted medical professional about trying cannabis to treat depression, anxiety, stress or insomnia.
Those who suffer from serious mental or physical illnesses can find cannabis helpful in relief from anxiety and an elevated mood. Some reports suggest 2 or 3 "puffs" is all it takes to calm down, relieve stress, and elevate mood.
How Cannabis Works
The pathology of depression is thought to be linked to hippocampal and prefrontocortical neural degeneration, neuroendocrine disturbances of the hypothalamic-pituitary-adrenal axis, and neurochemical deficits. (Bambico and Gobbi 2008)
Ultimately all antidepressants work by enhancing 5-HT neurotransmission, primarily in the hippocampus. Limonene (a terpene also found in cannabis) is a known anxiolytic and increases levels of dopamine via this mechanism. When neurons associated with dopamine fire, this controls the social defeat stress mechanism, a significant feature of depression. Limonene also appears to target the 5-HT1 receptor to increase the levels of serotonin in the prefrontal brain cortex. Linalool is also known for antidepressant and calming effect. ECS activity increases serotonergic and noradrenergic signaling, dampening the hypothalamic-pituitary-adrenal axis, and increasing neurogenesis and cellular resilience in the hippocampus. Depressed patients tend to have low anandamide and 2-AG blood levels and both are involved in ECS signaling.
Cannabis Pharmacy: The Practical Guide to Medical Marijuana. Michael Backes, fwd by Andrew Weil, M.D.
Research Studies Show How Cannabis Works with Depression
Antidepressant-like and anxiolytic-like effects of cannabidiol: a chemical compound of Cannabis sativa.
de Mello Schier AR, de Oliveira Ribeiro NP, Coutinho DS, Machado S, Arias-Carrión O, Crippa JA, Zuardi AW, Nardi AE, Silva AC1.
Anxiety and depression are pathologies that affect human beings in many aspects of life, including social life, productivity and health. Cannabidiol (CBD) is a constituent non-psychotomimetic of Cannabis sativa with great psychiatric potential, including uses as an antidepressant-like and anxiolytic-like compound. The aim of this study is to review studies of animal models using CBD as an anxiolytic-like and antidepressant-like compound. Studies involving animal models, performing a variety of experiments on the above-mentioned disorders, such as the forced swimming test (FST), elevated plus maze (EPM) and Vogel conflict test (VCT), suggest that CBD exhibited an anti-anxiety and antidepressant effects in animal models discussed. Experiments with CBD demonstrated non-activation of neuroreceptors CB1 and CB2. Most of the studies demonstrated a good interaction between CBD and the 5-HT1A neuro-receptor.
Endocannabinoid system dysfunction in mood and related disorders.
The endocannabinoid (EC) system is widely distributed throughout the brain and modulates many functions. It is involved in mood and related disorders, and its activity may be modified by exogenous cannabinoids. This article examines the therapeutic potential of cannabinoids in psychiatric disorders.
An overview is presented of the literature focused on the functions of the EC system, its dysfunction in mood disorders and the therapeutic potential of exogenous cannabinoids. We propose (hypothesize) that the EC system, which is homoeostatic in cortical excitation and inhibition, is dysfunctional in mood and related disorders. Anandamide, tetrahydrocannabinol (THC) and cannabidiol (CBD) variously combine antidepressant, antipsychotic, anxiolytic, analgesic, anticonvulsant actions, suggesting a therapeutic potential in mood and related disorders. Currently, cannabinoids find a role in pain control. Post mortem and other studies report EC system abnormalities in depression, schizophrenia and suicide. Abnormalities in the cannabinoid-1 receptor (CNR1) gene that codes for cannabinoid-1 (CB1) receptors are reported in psychiatric disorders. However, efficacy trials of cannabinoids in psychiatric disorders are limited but offer some encouragement.
Research is needed to elucidate the role of the EC system in psychiatric disorders and for clinical trials with THC, CBD and synthetic cannabinoids to assess their therapeutic potential.
The endocannabinoid system and the treatment of mood and anxiety disorders.
The central endocannabinoid system is a neuroactive lipid signaling system in the brain which acts to control neurotransmitter release. The expression patterns of this system throughout limbic regions of the brain ideally situate it to exert regulatory control over emotional behavior, mood and stress responsivity. A growing body of evidence unequivocally demonstrates that deficits in endocannabinoid signaling may result in depressive and anxiogenic behavioral responses, while pharmacological augmentation of endocannabinoid signaling can produce both antidepressive and anxiolytic behavioral responses. The aim of this review is to summarize current knowledge of the role of the endocannabinoid system in the etiology and treatment of mood and anxiety disorders, such as depression, anxiety and post-traumatic stress disorder. Collectively, both clinical and preclinical data argue that cannabinoid receptor signaling may be a realistic target in the development of a novel class of agent for the pharmacotherapy of mood and anxiety disorders.
https://www.ncbi.nlm.nih.gov/pubmed/19839936
Antidepressant-like effects of cannabidiol in mice: possible involvement of 5-HT1A receptors.
Cannabidiol (CBD) is a non-psychotomimetic compound from Cannabis sativa that induces anxiolytic- and antipsychotic-like effects in animal models. Effects of CBD may be mediated by the activation of 5-HT(1A) receptors. As 5-HT(1A) receptor activation may induce antidepressant-like effects, the aim of this work was to test the hypothesis that CBD would have antidepressant-like activity in mice as assessed by the forced swimming test. We also investigated if these responses depended on the activation of 5-HT(1A) receptors and on hippocampal expression of brain-derived neurotrophic factor (BDNF).
CBD (30 mg*kg(-1)) treatment reduced immobility time in the forced swimming test, as did the prototype antidepressant imipramine, without changing exploratory behavior in the open field arena. WAY100635 pretreatment blocked CBD-induced effect in the forced swimming test. CBD (30 mg*kg(-1)) treatment did not change hippocampal BDNF levels.
CBD induces antidepressant-like effects comparable to those of imipramine. These effects of CBD were probably mediated by activation of 5-HT(1A) receptors.
Putative role of endocannabinoid signaling in the etiology of depression and actions of antidepressants.
In the last few years, there have been several advances in the determination of the role of the endocannabinoid system in the etiology of depression and the functional actions of antidepressant drugs. Specifically, a deficiency in endocannabinoid signaling is sufficient to produce a "depressive-like" phenotype at the preclinical level (including changes in rewarding, emotional and cognitive behavior and biological changes such as increased HPA axis activity, impaired stress adaptation, reduced neurogenesis and altered serotonin negative feedback), and capable of inducing symptoms of depression in humans at a clinical level. In line with these findings, clinical populations diagnosed with depression are found to have reduced levels of circulating endocannabinoids and preclinical models of depression reveal a deficit in central endocannabinoid signaling. Moreover, facilitation of endocannabinoid signaling is sufficient to produce all of the behavioral and biochemical effects of conventional antidepressant treatments. Further, many forms of antidepressant treatments significantly alter endocannabinoid signaling, and in some of these cases this recruitment of endocannabinoid signaling is involved in the neuroadaptive effects of these treatments. Ultimately, these data present a compelling picture of the putative role of the endocannabinoid system in the processes sub serving both the development and treatment of depression.
Antidepressant-like effect of delta9-tetrahydrocannabinol and other cannabinoids isolated from Cannabis sativa L.
El-Alfy AT1, Ivey K, Robinson K, Ahmed S, Radwan M, Slade D, Khan I, ElSohly M, Ross S.
The antidepressant action of cannabis as well as the interaction between antidepressants and the endocannabinoid system has been reported. This study was conducted to assess the antidepressant-like activity of Delta(9)-THC and other cannabinoids. Cannabinoids were initially evaluated in the mouse tetrad assay to determine doses that do not induce hypothermia or catalepsy. The automated mouse forced swim (FST) and tail suspension (TST) tests were used to determine antidepressant action. At doses lacking hypothermic and cataleptic effects (1.25, 2.5, and 5 mg/kg, i.p.), both Delta(9)-THC and Delta(8)-THC showed a U-shaped dose response with only Delta(9)-THC showing significant antidepressant-like effects at 2.5 mg/kg (p<0.05) in the FST. The cannabinoids cannabigerol (CBG) and cannabinol (CBN) did not produce antidepressant-like actions up to 80 mg/kg in the mouse FST, while cannabichromene (CBC) and cannabidiol (CBD) exhibited significant effect at 20 and 200mg/kg, respectively (p<0.01). The antidepressant-like action of Delta(9)-THC and CBC was further confirmed in the TST. Delta(9)-THC exhibited the same U-shaped dose response with significant antidepressant-like action at 2.5 mg/kg (p<0.05) while CBC resulted in a significant dose-dependent decrease in immobility at 40 and 80 mg/kg doses (p<0.01). Results of this study show that Delta(9)-THC and other cannabinoids exert antidepressant-like actions, and thus may contribute to the overall mood-elevating properties of cannabis.
Circulating endocannabinoids and N-acyl ethanolamines are differentially regulated in major depression and following exposure to social stress.
Central endocannabinoid signaling is known to be responsive to stressful stimuli; however, there is no research to date characterizing the effects of stress on peripheral endocannabinoid content. The current study examined serum content of the endocannabinoid ligands N-arachidonylethanolamide (anandamide; AEA) and 2-arachidonoylglycerol (2-AG), and the non-cannabinoid N-acyl ethanolamine (NAE) molecules palmitoylethanolamide (PEA) and oleoylethanolamide (OEA) under basal conditions, immediately following the Trier Social Stress Test (TSST), and 30 min thereafter, in 15 medication-free women diagnosed with major depression, and 15 healthy matched controls. Basal serum concentrations of AEA and 2-AG, but not PEA or OEA, were significantly reduced in women with major depression relative to matched controls, indicating a deficit in peripheral endocannabinoid activity. Immediately following the TSST, serum 2-AG concentrations were increased compared to baseline; serum AEA concentration was unchanged at this time point. Serum concentrations of PEA and OEA were significantly lower than baseline 30 min following the cessation of the TSST. The magnitude of these responses did not differ between depressed and control subjects. These are the first data to demonstrate that the peripheral endocannabinoid/NAE system is responsive to exposure to stress.
Serum contents of endocannabinoids are correlated with blood pressure in depressed women.
Depression is known to be a risk factor for cardiovascular diseases but the underlying mechanisms remain unclear. Since recent preclinical evidence suggests that endogenous agonists of cannabinoid receptors (endocannabinoids) are involved in both cardiovascular function and depression, we asked whether endocannabinoids correlated with either in humans.
Resting blood pressure and serum content of endocannabinoids in ambulatory, medication-free, female volunteers with depression (n = 28) and their age- and ethnicity-matched controls (n = 27) were measured. In females with depression, both diastolic and mean arterial blood pressures were positively correlated with serum contents of the endocannabinoids, N-arachidonylethanolamine (anandamide) and 2-arachidonoylglycerol. There was no correlation between blood pressure and endocannabinoids in control subjects. Furthermore, depressed women had significantly higher systolic blood pressure than control subjects. A larger body mass index was also found in depressed women, however, it was not significantly correlated with serum endocannabinoid contents.
This preliminary study raises the possibility that endocannabinoids play a role in blood pressure regulation in depressives with higher blood pressure, and suggests an interrelationship among endocannabinoids, depression and cardiovascular risk factors in women.
The therapeutic potential of the endocannabinoid system for the development of a novel class of antidepressants.
The endocannabinoid system is a neuromodulatory system which is known to regulate emotional, cognitive, neurovegetative and motivational processes. Substantial evidence has accumulated implicating a deficit in endocannabinoid in the etiology of depression; accordingly, pharmacological augmentation of endocannabinoid signaling could be a novel target for the pharmacotherapy of depression. Within preclinical models, facilitation of endocannabinoid neurotransmission evokes both antidepressant and anxiolytic effects. Similar to the actions of conventional antidepressants, enhancement of endocannabinoid signaling can enhance serotonergic and noradrenergic transmission; increase cellular plasticity and neurotrophin expression within the hippocampus; and dampen activity within the neuroendocrine stress axis. Furthermore, limbic endocannabinoid activity is increased by both pharmacological and somatic treatments for depression, and, in turn, appears to contribute to some of the neuroadaptive alterations elicited by these treatments. These preclinical findings support the rationale for the clinical development of agents which inhibit the cellular uptake and/or metabolism of endocannabinoids in the treatment of mood disorders.
Cannabidiol induces rapid-acting antidepressant-like effects and enhances cortical 5-HT/glutamate neurotransmission: role of 5-HT1A receptors.
Cannabidiol (CBD), the main non-psychotomimetic component of marihuana, exhibits anxiolytic-like properties in many behavioral tests, although its potential for treating major depression has been poorly explored. Moreover, the mechanism of action of CBD remains unclear. Herein, we have evaluated the effects of CBD following acute and chronic administration in the olfactory bulbectomy mouse model of depression (OBX), and investigated the underlying mechanism. For this purpose, we conducted behavioral (open field and sucrose preference tests) and neurochemical (microdialysis and autoradiography of 5-HT1A receptor functionality) studies following treatment with CBD. We also assayed the pharmacological antagonism of the effects of CBD to dissect out the mechanism of action. Our results demonstrate that CBD exerts fast and maintained antidepressant-like effects as evidenced by the reversal of the OBX-induced hyperactivity and anhedonia. In vivo microdialysis revealed that the administration of CBD significantly enhanced serotonin and glutamate levels in vmPFCx in a different manner depending on the emotional state and the duration of the treatment. The potentiating effect upon neurotransmitters levels occurring immediately after the first injection of CBD might underlie the fast antidepressant-like actions in OBX mice. Both antidepressant-like effect and enhanced cortical 5-HT/glutamate neurotransmission induced by CBD were prevented by 5-HT1A receptor blockade. Moreover, adaptive changes in pre- and post-synaptic 5-HT1A receptor functionality were also found after chronic CBD. In conclusion, our findings indicate that CBD could represent a novel fast antidepressant drug, via enhancing both serotonergic and glutamate cortical signalling through a 5-HT1A receptor-dependent mechanism.
https://www.ncbi.nlm.nih.gov/pubmed/26711860
Dosing with Cannabis
THC is the cannabinoid which gives you a "psychedelic high" where as CBD and other cannabinoids do not. Some people enjoy this feeling, however if you have never tried marijuana before you should start with smaller doses of THC and after some time only increase THC dosing if necessary. Some people may accidentally take too strong of a high THC dose and may feel like they are experiencing anxiety, so finding a preferred strain is important when purchasing medical cannabis. If you find this is happening to you, next time you get that "anxiety feeling" from consuming too high of a dose all you need to do is tell yourself to sit quietly, calm down and breathe. Take deep, but relaxing breaths. Close your eyes if you can and remain calm and relaxed and take deep breaths. Doing this exercise will help your heart calm down and then your thoughts will follow. This small meditative move should help to calm anyone down. The next step would be to give yourself a distraction. Read a book, listen to music, or play with your pets or kids. Watch a comedy and drink plenty of water.
A light dose of THC such as 2.5mg up to 5mg inhaled or taken sublingually may be useful in elevating mood. Light doses of CBD 5mg to 10mg is recommended for anxiety accompanying depression.
(PTSD patients should avoid cannabis with the terpen PINENE which may interfere with memory remodeling and MYRCENE during the day which may contraindicate suicidal ideas)
Orally a ratio with anything that offers a higher CBD ratio such as CBD:THC 10:1 or higher. Doses of 5 mg of CBD in the morning and afternoon can be used throughout the day, but the last dose should occur no later than 5pm so it does not disrupt sleep. Light doses of THC such as 2.5mg-5mg can be taken to lift mood and still function. If insomnia is a problem then heavier doses of THC can be taken orally before bed. (Indica strains are best for sleep)
Inhaled CBD and THC can be helpful in lifting mood. A few puffs is all it takes. If shopping for cannabis at the dispensary is an option for you, look for strains with Limonene and Linalool.
We hope this information helps you get an understanding of how cannabis reacts in your brain and plays a crucial role in help with depression. Cannabis taken alone may not help. But adding cannabis to a daily regimen of trying to get your state-of-mind healthier will help out a lot! For some patients, it helps to take cannabis before talking to their therapist or psychiatrist, because they feel that being high while talking can help them feel more comfortable about opening up, and become more understanding of circumstances, which helps them work with their therapist to make better connections, mentally.
Don't forget to talk to a trusted medical professional about cannabis as an option and do your own research to see if it will work for you. If you have never tried cannabis before; Remember, start low and go slow with doses, look for treatments with CBD as well as THC. They both work well together.
I hope you can find the peace you have been looking for.
