There is rising interest in using medical cannabis for mental health conditions such as depression. This is based on studies that suggest cannabis can increase quality of life, having a positive effect on the symptoms of depression. Cannabis has also been shown to aid in chronic illnesses like multiple sclerosis, cancer and chronic pain. 

Currently, depression is treated with traditional antidepressants and talking therapies. With over 83 million estimated antidepressant prescriptions per year, it is important to consider any and all drug interactions with this type of medication; especially when it comes to new drugs of interest that also work in the brain, like cannabis. 

Introduction

Cannabis is gaining interest in the medical community for treatment-resistant mental health issues. Cannabis has been shown to help relieve symptoms of depression in some but has also been shown to be detrimental to the symptoms of others.^1,2 Because of this, the final verdict from the scientific community as to whether or not cannabis can directly help with depression is still unclear. Hence, medical cannabis is not prescribed to patients with depression in the UK. It can be, however, prescribed for other medical problems. 

Patients with depression are usually prescribed antidepressant medications, commonly:

• Selective serotonin reuptake inhibitors (SSRIs)
• Serotonin-Noradrenaline reuptake inhibitors (SNRIs)
• Tricyclic antidepressants (TCAs)

All of these medicines work by increasing concentrations of “happy” hormones in the brain; chemicals such as serotonin, noradrenaline and dopamine. The result is in some cases an improvement or complete alleviation of depression symptoms like low mood, lack of motivation or suicidal thoughts. 

Why would you take cannabis and antidepressants together?

There are many different circumstances under which someone on traditional antidepressants may seek out medical cannabis. There are some reports of cannabis helping to relieve symptoms of depression.¹ This may lead some to believe that cannabis can be used as an additive to traditional antidepressant therapy to improve symptoms further. 

Moreover, depression is closely linked to chronic illness.³ Therefore, some individuals may think to co-administer cannabis and antidepressant medications for two different conditions. Examples of circumstances in which one might consider medical cannabis use whilst on traditional antidepressants include:

• Severe, rare or drug-resistant epilepsy⁴
• Cancer⁵
• Treatment-resistant muscle stiffness and spasms in multiple sclerosis⁶
• Chronic pain⁷

Why are drug interactions important to know?

Drug interactions can vary dramatically depending on many different variables. Some drugs can work together, even promoting each other’s effects. They can also work in opposing directions against each other. In other instances, drug groups do not interact at all; they work on different systems doing their own thing. In simple terms, based on how they interact, some drugs can be taken together and some cannot or should not be. Therefore drug interactions are important to know, especially as some interactions can cause severe damage to the body and even death. 

How medical cannabis works in the body

Medical cannabis works on the endocannabinoid system, which plays an important role both in the brain and around the body. The chemicals responsible for signalling in the endocannabinoid system are called cannabinoids. Cannabis is composed of two main cannabinoids; tetrahydrocannabinol (THC) and cannabidiol (CBD). Signalling within the endocannabinoid system takes part in many neurological processes like brain development, pain, learning and memory.⁸ Outside of the brain, the endocannabinoid system plays a part in hormonal balance, the immune system and the autonomic nervous system.⁹

In summary, the effects of medical cannabis are not isolated to a particular area and affect the whole body, making drug interactions something to look out for. 

How antidepressants work in the body

We do not know exactly how depression arises. The working theory that supports the use of antidepressants is that depression is caused by a deficit in specific chemicals in the brain and consequent deficits in specific brain activity. The main purpose of antidepressants is, therefore, to increase hormones that are associated with the signalling of happiness, like serotonin, noradrenaline and dopamine. 

A bit about signalling 

Antidepressants focus on helping the brain to signal wellbeing better; But what does this mean and how do some hormones help signals transmit from neuron to neuron?

In the normal state, chemicals called neurotransmitters (such as serotonin and noradrenaline) are released from one neuron (the presynaptic neuron, at the pre-synapse), into a space called the synaptic cleft, through which they pass to the next neuron (the postsynaptic neuron, at the post-synapse). To promote healthy signalling, the synaptic cleft cannot be full of neurotransmitters all of the time. Hence, if unused by the postsynaptic neuron, they are taken back in and recycled by the presynaptic neuron which releases them. This is called reuptake. It is theorised that unsuccessful signal transmissions of serotonin, noradrenaline and dopamine cause depression. 

SSRIs and SNRIs

SSRIs are the most commonly prescribed antidepressants. SSRIs and SNRIs are different classes of drugs that essentially perform the same task but through different mechanisms. They both prevent serotonin and/or noradrenaline from being reabsorbed into presynaptic nerve endings, thus increasing the available concentration of these chemicals for signalling. In plain terms, they make serotonin and noradrenaline signalling easier for the brain to do.  

TCAs

Tricyclic antidepressants essentially do the same thing as SNRIs. They prevent the reuptake of serotonin and noradrenaline into the nerve they were released from, thus promoting signalling. However, they are an older class of drugs that do not target serotonin reuptake well and have a larger number of off-target effects. 

Common interactions between drugs

Drug-drug interactions are not difficult to predict if the mechanisms of action and off-target side effects of both drugs are known. Potential interactions can arise due to the following:

• Additive or opposing effects: Drug effects can add up or cancel out 
• Absorption: One of the drugs may either prevent or increase the absorption of the other into the bloodstream or affected tissue
• Distribution: One of the drugs may prevent the other from reaching where it is supposed to be in the body
• Metabolism: One of the drugs can prevent or increase the breakdown of the other
• Excretion: One of the drugs can prevent or increase the rate of elimination of the other from the body

Interactions between cannabis and antidepressants

Due to the fact that medical cannabis and traditional antidepressants both work in the brain, they have the potential to interact. Below we will explore the possible interactions of cannabis with specific antidepressants. 

Cannabis and SSRIs

The use of cannabis with SSRIs is usually not recommended. The CBD in cannabis inhibits the proteins which are responsible for the breakdown of two commonly prescribed antidepressants; citalopram and escitalopram.¹⁰ This can potentially lead to an increase in side effects like sedation and cognitive impairment. In some cases, taking high doses of cannabis with SSRIs can mean that the level of serotonin in the brain gets too high.¹¹ 

Although in depression, we want to see an increase in serotonin concentrations, everything in the body exists in balance. Therefore, when there is too much serotonin, individuals can experience a severe condition called serotonin syndrome, which results in symptoms like:

• Confusion
• Agitation
• Muscle twitching
• Sweating while shivering
• Diarrhoea 
• Seizures 
• Irregular heartbeat
• Loss of consciousness 

Cannabis and SNRIs

Like SSRIs, SNRIs are also metabolised by molecules which are inhibited by cannabis. This means that medical cannabis can increase the amount of drug in the blood and cause unpleasant side effects.¹² Because SNRIs also target serotonin, there is also a risk of serotonin syndrome if doses are high enough. Other side effects of the mixing of cannabis with SNRIs include:¹²

• Low blood salt levels (hyponatraemia)
• Abnormal bleeding 
• Changes to the heart rhythm 

Cannabis and TCAs 

Tricyclic antidepressants are also at risk of impaired metabolism with cannabis use. The result is an additive effect and an increase in side effects.¹³ In one case, a patient who took a tricyclic antidepressant with cannabis was admitted to hospital with a potentially fatal “racing heart”, which was measured to beat at 300 beats per minute.¹⁴ Other symptoms may include:

• Dry mouth
• Blurry vision
• Constipation and problems urinating
• Drowsiness 
• Dizziness
• Excessive sweating

Considerations 

The interactions of medical cannabis with antidepressants are not well established. However, it is important to always consult with your healthcare professional before starting new therapies due to the potential for drug interactions. 

Summary

Drug interactions are important to consider in medicine, as they can increase side effects or even be fatal. The interaction between cannabis and antidepressants has not yet been studied extensively. Cannabis affects the proteins responsible for the breakdown of some classes of antidepressants, which include SSRIs, SNRIs and tricyclic antidepressants. This results in higher concentrations of the drug in the body and an increased risk of side effects. In some cases, the mixing of the drugs can cause serotonin syndrome, which is a potentially life-threatening condition that is a result of too much serotonin in the brain. The co-administration of cannabis and antidepressants has also caused dangerous increases in heart rate. Overall, it is important to consult with a doctor in the case of starting new drugs, especially if they are to be taken in combination with others.