Cannabis and mental health

Cannabis and mental disorders: the dilemma of cause and effect

Medical cannabis has been gaining increasing acceptance in scientific and medical circles around the world thanks to evidence-based clinical studies showing the therapeutic potential of cannabis for the treatment of chronic pain and multiple sclerosis, or as a palliative in cancer treatments, among other medical conditions [1].

But in the field of mental health, there is still far from sufficient scientific evidence of its therapeutic efficacy. In fact, the idea generally accepted by most health professionals is the reverse: cannabis leads to a deterioration of mental health.

A recent article by the National Institute on Drug Abuse (NIDA, 2023) [2] reports that, while there is evidence linking cannabis use to an earlier onset of psychosis in people predisposed to psychotic disorders, including schizophrenia, and a worsening of symptoms in people already suffering from psychosis, it is also true that people with mental disorders turn to cannabis to alleviate their symptoms, known as the 'self-medication hypothesis'. Some studies have thus found that many cannabis users experience improvements in their levels of anxiety and depression, and even use cannabis to reduce these emotional problems [3].

It is true that cannabis use can be detrimental to mental health. This is also echoed in the above-mentioned NIDA article, which notes that this negative relationship is modulated by a number of risk factors, including: the amount of drug used, the frequency of use, the potency (THC content) and type of cannabis product, and the age of the person at the time of first use.

However, this does not negate the fact that cannabis can be used therapeutically if the medical prescription is accompanied by strategies to minimise the above-mentioned risk factors. Drug risk and harm reduction programmes have already proven to be effective in this regard. It therefore remains entirely justified, at this point, and given the controversy discussed above about the direction of causation between cannabis use and mental health, to ask whether medical cannabis could improve mental health.

There is more than sufficient evidence of its therapeutic potential in this area, based on both laboratory and observational studies. A comprehensive review can be found in Amigó and Miravete (2024) [4].

The biochemistry of cannabis and mental health

It is interesting to note that a number of biochemical laboratory studies observe an imbalance of the endocannabinoid system, with a deficit of endocannabinoids, in different mental health problems. Thus, low serum levels of anandamide (ADA) and 2-arachinoyl-glycerol (2-AG) have been found in women diagnosed with major depression who were not on medication [5,6].

The pathophysiology of Post Traumatic Stress Disorder (PTSD) has also been linked to the endocannabinoid system, with brain-imaging studies showing an overexpression of CB1 receptors in the brains of people with PTSD compared to controls, as well as a significant reduction in the level of peripheral ADA [7].

If there is a deficit of endocannabinoids in mental disorders, it is logical to suppose that a supply of external cannabinoids can alleviate this deficit and thus improve mental health.

Thus, it has been found that the anxiolytic effects of CBD have been associated with its action on the limbic system: amygdala, hypothalamus, hippocampus, posterior cingulate gyrus and left parahippocampal gyrus, which are areas of the brain related to the pathophysiology of anxiety [8]. Increased serum levels of ADA and 2-AG have also been found in patients with major depression treated with electroconvulsive therapy [9].

Moreover, ADA levels in cerebrospinal fluid and blood in schizophrenic patients have been found to be related to psychotic symptoms [10,11], and ADA levels have also been found to be a function of frequency of consumption in these patients [12]. In these cases, the compensatory physiological mechanisms of the endocannabinoid system play an important role.

These results lead us to deduce that, in fact, with the contribution of the cannabinoids provided by the plant, it is possible to improve mental problems such as anxiety, depression and psychotic disorders, among others, and that, therefore, medical cannabis should also incorporate the improvement of mental health as a therapeutic objective.

Medical cannabis, mental health and quality of life: the scientific evidence

In a study of 129 patients with treatment-resistant depression who were treated with medical cannabis at Sapphire Medical Clinics (the only clinic that requires patients to be registered with the UK Medical Cannabis Registry), a reduction in the severity of depression was observed at months 1, 3 and 6 of follow-up [13]. In addition, medical cannabis improved neurocognitive functioning in bipolar patients as well as alleviating their symptoms [14,15]. A controlled cohort study showed a reduction in the severity of PTSD symptoms using CBD products [16]. In two randomised controlled studies of CBD-rich medical cannabis products in schizophrenic patients, a decrease in positive psychotic symptoms, such as hallucinations and delusions, was observed, as well as an improvement in cognitive performance and an increase in ADA [17,18].

All this data – not only from anecdotal studies, but also observational and more methodologically demanding ones such as some controlled studies – indicates that favourable results for the improvement of mental health can be obtained from the use of medical cannabis.

Furthermore, at the end of the 20th century, the WHO coined the term "health-related quality of life" to emphasise the importance of promoting sufficient quality of life, especially in patients with chronic diseases. Therefore, the main objective of medical treatment is not just curing the disease: quality of life becomes of primary importance to achieve the complete physical and psychological improvement of the patients whose prognoses are more negative or who have chronic diseases.

Medical cannabis has also been used with the objective of improving quality of life. Thus, in a previously cited study of patients with treatment-resistant depression, in addition to improved levels of depression, a significant reduction in levels of general anxiety, improved sleep quality and health-related quality of life (as measured by EQ-5D-5L) was observed at baseline and after 1, 3 and 6 months of treatment [13].

We have also conducted a study on medical cannabis and the improvement of quality of life. This is a study carried out by the University of Valencia, together with the Terapéuticas Hierbas Castelló association and the collaboration of the Fes-Ho-Bé! association and Fundación CANNA. It is an observational study which followed 22 patients with different diseases (cancer, fibromyalgia, chronic pain, etc.) for 7 months. An initial diagnostic and anamnestic session of the patient's current health status was carried out by the medical team, and two health-related quality of life questionnaires (EQ-5D-5L and SF-36) were administered. During the following 6 months, a monthly follow-up of their progress was carried out, assessing their quality of life using the same instruments used in the diagnostic session.

The results were very clear. Patients significantly improved their health-related quality of life in all dimensions measured by the instruments used. EQ-5D-5L measures 5 dimensions: mobility, self-care, usual activities, pain/discomfort, and anxiety/depression, plus a health scale. Patients improved in every dimension over 6 months. SF-36 measures 8 dimensions of quality of life, from which two major dimensions are derived: physical health (physical functions and relevant limitations to role activities, pain, general health) and mental health (vitality, social activities, limitations to role activities due to emotional health, general mental health). However, in all follow-up sessions, the improvement in the mental health dimension was clearly greater (from a mean score of 33.06 to 41.40) than the improvement in the physical health dimension (from a mean score of 32.21 to 37.36). At this point, it is important to highlight that health-related quality of life has a very important mental health component: this concept, which – as we mentioned above – was proposed by the WHO, is integrated and holistic, understanding health in general as the sum of physical and mental health. It should also be noted that in some patients there was a slight decrease in quality of life in the last two months. If we consider that these two months coincided with the beginning of the COVID-19 pandemic, we can conclude that medical cannabis had a sufficiently positive impact on the improvement of quality of life despite the unfavourable conditions of the pandemic.

The procedure carried out in this study is described in detail in Amigó and Miravete (2024) [4].

With all that has been said in this article, it is perfectly clear that medical cannabis should not only be used for the treatment of illnesses and the improvement of physical health, but also for the improvement of mental health. A multitude of evidence in observational and controlled studies indicates the way forward in the research on medical cannabis and mental health, and its use for the treatment of mental disorders, in the coming years.

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