Some research suggests that marijuana smokers are diagnosed with depression more often than non-smokers, particularly those who use marijuana regularly or in large amounts. However, it does not appear that marijuana directly causes depression. Genetic, environmental, or other factors that trigger depression are also likely to lead to marijuana use. Some people with depression may use marijuana as a way to detach from their depressive symptoms. Heavy users may appear depressed as a result of the drug’s dampening effects on feelings and emotions.
A study published in the Journal of Affective Disorders indicates that smoking marijuana significantly reduces levels of depression, anxiety, and stress in the short term, but then worsens them in the long term. Another JAMA Psychiatry study found that marijuana use before the age of 18 increases the risk of depression, suicidal ideation, and attempts between the ages of 18 and 32.
However, not all studies are negative because according to an analysis carried out by Mangieri R. (2008), in rodents modified to suffer from depression, they showed altered levels of endogenous cannabinoids and the CB1 cannabinoid receptor, implicating this system as a possible etiological cause of depression. Thus, when cannabinoid receptor signaling was enhanced, there was an improvement in the characteristic symptoms of the disease.
On the other hand, Jiang W (2005) considers cannabinoids to be the only illicit drug capable of promoting neurogenesis in the hippocampus after chronic administration. This increase in neurogenesis appears to be associated with anxiolytic-antidepressant effects similar to those produced by high-dose HU210 (synthetic cannabinoid) treatment. Where they have complementary help if they are undergoing treatment for depression is when cannabinoids are used to alleviate some of its characteristic symptoms: anxiety, stress, lack of appetite, or insomnia.
The use of CBD could represent a good therapeutic tool due to its different mechanisms of action, its effects, and because it is not psychoactive. The properties of CBD can be beneficial in relieving different symptoms of depression:
1- Indirectly stimulates the CB1 and CB2 endocannabinoid receptors which are involved in the regulation of neurotransmitters related to depression.
2- Stimulates 5-HT1a receptors, helping to regulate serotonin and dopamine levels to promote emotional stability.
3- It stimulates the functioning of the Endocannabinoid System, facilitating its work in maintaining the psycho-physical balance, in the management and reduction of stress, and in the maintenance of mental and physical energy.
4- It has an anxiolytic and antipsychotic effect that is great help for those suffering from an anxious-depressive syndrome or psychiatric-type symptoms.
5- It has a relaxing effect on a mental and physical level, favoring a good quality of sleep and rest and the reestablishment of natural circadian rhythms.
6- Its neuroprotective and antioxidant effect favors neuronal plasticity and cognitive functions affected by depressive states.
7- In case of suffering from depression associated with physical ailments of an inflammatory type that cause pain, the anti-inflammatory and analgesic effect of CBD could also be of great help.
We can say that the previously stated points are supported by scientific studies, including one from researcher, Juan Fernando Muñoz Ramírez, entitled, “El cannabidiol y sus indicaciones en psiquiatría” (Cannabidiol and Its Indications in Psychiatry.)
CBD is the second largest constituent of cannabis in addition to THC. It does not have the psychotropic effects of THC and can antagonize them. CBD affects anxiolytics by regulating various neuroendocrine processes in the stress response cascade and has potential uses in psychiatry: disorders of anxiety, dysfunctional behaviors in disorders of the autism spectrum, schizophrenia, addictions, and sleep disorders. It has excellent tolerability in all age ranges and does not induce dependence. It is a substance of great utility as a pharmacological option in psychiatry. More clinical trials are needed to better support this treatment option.
Additionally, CBD stimulates synaptic plasticity and neurogenesis which also plays a role in the development and treatment of depression. Some animal models have shown promising results. A mouse model of depression showed a significant antidepressant-like effect after CBD administration. The animals also showed greater participation in pleasurable activities. However, in humans, very limited studies are available. In vitro, CBD was found to be a microglial stabilizer similar to the drug lithium which could be beneficial for depression and mood stabilization.
In humans, there are only a few published case studies of individual patients with a history of depression who have previously been on traditional selective serotonin reuptake inhibitor (SSRI) treatment who successfully tried CBD products and experienced significant improvement in their depressive symptoms. Caution is warranted with these studies. The studies are using a controlled form of CBD without any significant THC content. The studies also have small patient numbers and the follow-up windows are short. Significant toxic effects have been reported with the use of CBD, one of them being more depressive and even suicidal ideation.
The package insert for the FDA-approved form of CBD Epidiolex lists depression and suicidal ideation as possible adverse reactions. In the largest placebo-controlled clinical trial among 27,863 Epidiolex-treated patients and 16,029 placebo-treated patients, the risk of suicidal ideation was increased by 1 in 530 patients with four suicides occurring in the Epidiolex-treated group versus none in the Epidiolex-treated placebo group. No compatible data is available comparing over-the-counter CBD to placebo with respect to increased risk of suicidality.
In the study, “Papel Terapéutico del Cannabidiol en el tratamiento de los trastornos de ansiedad. Análisis de la evidencia clínica y preclínica” (Therapeutic Role of Cannabidiol in the Treatment of Anxiety Disorders), analysis of the clinical and preclinical evidence carried out by the researcher, Carlota Carmona Barragán, provided interesting conclusions that support the therapeutic use of CBD in therapies for anxiety disorders. Although, we must make it clear that these conclusions are not definitive as more studies are needed to be able to delve into the subject and thus obtain definitive results.
In general terms, clinical and preclinical evidence supports the anxiolytic role of CBD as a potential alternative treatment pathway for anxiety disorders. Preliminary evidence in human clinical trials suggests an anxiolytic effect of the CBD. In addition, CBD has amply demonstrated a good safety profile and tolerance. It shows no potential for abuse or dependency.
For this reason, CBD could be combined with existing psychological therapies by increasing extinction and interfering with the reconsolidation of fear memory. By raising anandamide levels, FAAH inhibitors may also be a potential therapeutic option to consider.
“The Impact of Cannabidiol on Psychiatric and Medical Conditions” is an analysis that pointed out that “anxiety and PTSD are very common psychiatric disorders in the US and are associated with substance use”. While cannabis with its THC content has shown to be anxiogenic during intoxication as well as withdrawal, CBD has been discussed to have some anxiolytic potential. In animal studies, the systemic administration of CBD had caused a decrease in neurons associated with fear (c-Fos positive neurons) and a direct infusion of CBD in the amygdala neurons has led to decreased anxiety-related behaviors. Another animal model showed that CBD modifies the cerebral blood flow in brain areas that play a role in anxiety symptoms: amygdala, hippocampus, hypothalamus, as well as cingulate cortex.
Several human studies have shown positive results of CBD in anxiety conditions as well. The effect of CBD on the amygdala was studied in brain imaging studies and showed a decrease in activation in the amygdala after administration of CBD. A placebo-controlled study by Crippa et al showed a decrease in social anxiety symptoms but also sedation in a small group of 10 patients receiving CBD. The patients in this clinical study were treatment naive and with only 10 participants, the study was small.
Another study by Bergamaschi among 24 treatment-naive patients looked at the effect of 600 mg CBD during a public speaking test and noticed a reduction in anxiety, cognitive impairment, as well as discomfort in speech performance. Furthermore, a study by Das et al included 48 healthy volunteers evaluated for anxiety provoking electric shock anticipation by receiving either pure CBD without THC or placebo. The results showed that CBD increases extinction and might play a role in therapeutic approaches for anxiety disorder treatment.
The lifetime prevalence of PTSD in the US is about 6.1% of the population. The treatment has mostly consisted of antidepressants as well as Prazosin for nightmares. CBD has been reported in case-controlled studies to be beneficial for nightmare symptoms associated with PTSD. In another small study of 11 patients with PTSD, oral CBD was administered open-labeled. The patient’s PTSD symptoms were initially evaluated and on consecutive days up to 8 weeks after utilizing the PCL-5 test and score. Ninety-one percent of the patients reported a decrease in nightmare symptoms. None of the patients reported side effects.
However, despite these studies with small patient numbers that utilized the pure form of CBD, there are also several case reports of CBD-induced anxiety symptoms as a toxic side effect from the substance.
Risk of CBD Use
It is possible to ingest amounts of CBD that cause a fatal overdose, but very large doses are required for that to occur in humans. CBD toxicity levels can be found on the Federal Government Toxicology Data Network. The risk of lethality with toxic substances is generally measured in LD50 which is the amount of substance necessary to kill 50% of the population.
There are three studies cited regarding the determination of the LD50 of CBD: 1) In 1946, the LD50 of CBD in dogs was determined to be greater than 254 mg per kg of body weight when administered intravenously. 2) In 1975, an LD50 in mice was established at 50 mg per kg of body weight when administered intravenously. 3) In 1981, a report in Toxicology and Applied Pharmacology showed the LD50 for CBD to be 212 mg per kg of body weight when administered intravenously to monkeys.
More recently, a 2011 article in the journal “Current Drug Safety” observed toxic levels of CBD in rhesus monkeys when administered orally. Doses of more than 200 mg per kg of body weight were found to be fatal in some monkeys due to respiratory arrest and heart failure, while 300 mg per kg of body weight resulted in “rapid death”.
For reference, consider an “average size” human of 75 kg (approximately 165 pounds). Based on these numbers, it would take approximately 18,750 mg (18.75 g) of CBD consumed in a very short period of time for potentially fatal effects to occur. By comparison, most typical CBD oil users consume no more than 100 mg of the compound and that’s over the course of a full day.
Although the findings are promising, future research is needed to clarify the pharmacological targets through which CBD exerts its anxiolytic effect. It is also It is necessary to carry out clinical trials with a larger sample size, including groups with placebo control to establish a dose-response relationship between levels. Finally, it only remains to wait as scientists continue working to discover both the benefits and the risks of using cannabis in diseases such as depression and how this type of pathology can be cured with the use of the plant and its derivatives.
We hope that this blog will help provide you with more knowledge about the medicinal use of cannabis. We always seek to deliver quality and accurate information to keep you informed in the correct way. In addition, we encourage you to consult with your treating doctor for a possible medical cannabis treatment if you suffer from depression and only if the specialist authorizes you to start using weed for your recovery.
Do not forget that at Blimburn Seeds, we have varieties and cannabis seeds that are free of THC and even CBD. We are talking about our genetics that are rich in CBG which do not produce psychoactive effects. Those suffering from depression can consult their doctor regarding the cultivation of plants for a therapeutic process.