Introduction

Have you ever wondered how the use of cannabis may be affecting your brain? Cannabis, commonly referred to as weed or marijuana, is a plant-based drug derived from the dried leaves, stems, flowers, and seeds of the cannabis plant, Cannabis sativa L.¹ Cannabis contains active chemicals, called cannabinoids, that can have intoxicating drug-like effects throughout the body, influencing people's moods and thoughts, and altering their perceptions.² Cannabis affects both the central nervous system (CNS) and the immune system. With cannabis use continuing to grow in recent years, both for medicinal and recreational purposes, it is time to explore what really goes on under the surface and inside your head. The brain is composed of a series of different signalling pathways, made up of interconnected neurons that transmit signals and regulate processes within the nervous system. These signals, or neuronal communications, occur through the release of chemical messengers known as neurotransmitters.³ Amongst these neurotransmitters, serotonin is involved in multiple functions including attention, mood regulation, appetite, and sleep,.³ The consumption of cannabis is thought to influence the levels of serotonin. Therefore, could cannabis be affecting the very chemistry that controls how you feel? Dive into this article to explore and uncover how cannabis can affect serotonin levels and the impact it is having, discovering what this means for both your well-being and mind. 

Understanding serotonin 

Serotonin is a neurotransmitter and regulatory hormone, known as 5-hydroxytryptamine (5-HT), which plays an integral physiological role in the human body, regulating various activities; these include regulating behaviour, mood, anxiety and memory.⁴ Large concentrations of serotonin neurons are mainly be found in a series of nuclei known as the raphe nuclei, located in the brainstem. Projections from these nuclei can either descend to the spinal cord, controlling pain transmission, or ascend to different areas of the brain, including the cortex, hippocampus and the hypothalamus.³

As individuals, it is important to make sure our serotonin levels remain normal because levels that are too high or too low can cause both physical and psychological health problems. Over the years, serotonin has been attributed the title of the body's “feel good” chemical because balanced serotonin levels allow us to feel more emotionally stable, happier, calmer, and to remain focused.⁵ However, inefficient or decreased levels of serotonin are considered to be central to the cause of anxiety, depression, and other psychological disorders, such as:⁴

• Panic disorders
• Schizophrenia
• Obsessive compulsive disorder (OCD)
• Suicidal behaviour

Excessive levels of serotonin in the body can cause various pathological symptoms; this is known as serotonin syndrome (or toxicity), where excessive serotonin activity occurs in the CNS arising from various sources, including intentional drug overdoses, drug interactions, and therapeutic medication use. Cannabis and its active compounds 

Cannabis is a drug derived from the dried leaves, stems, flowers and seeds of the Cannabis sativa L plant.¹ Cannabis contains active chemicals called cannabinoids; research has shown cannabis contains at least 125 different cannabinoid chemicals, and around 300 non-cannabinoid chemicals.¹ People use the different types of cannabinoids for different purposes, including medicinal and recreational. Amongst the different varieties, there are two main types of cannabinoids:

Delta-9-tetrahydrocannabinol (THC) 

This type of cannabinoid is responsible for the psychoactive effects commonly associated with cannabis. THC binds to cannabinoid receptors located in the brain, which affects both the release and uptake of different neurotransmitters, for example dopamine and serotonin this interference causes both the therapeutic benefits, such as pain relief, and the psychoactive effects. The intoxicated state cannabis causes is often sought after by recreational users, which can lead to addiction, temporarily altering people's thoughts, perceptions and moods.¹,⁶ THC can cause certain adverse effects, including:

• Hallucinations
• Confusion
• Headaches 
• Paranoia
• Dysphoria

In more severe cases, both seizures and seizure-like activity have been reported.⁷ Despite this, THC has recently started to be used to both manage and treat chemotherapy-induced nausea, vomiting, and stimulate appetite; this shines light on the recent change in the utilisation of cannabis, going from being predominantly used for recreational purposes, to more recently being used for potential medicinal applications.⁸

Cannabidiol (CBD)

This is the non-psychoactive component of cannabis, meaning CBD does not produce psychoactive effects on people. The absence of psychoactivity is one of the main factors as to why CBD is of growing interest for its potential therapeutic abilities. Differently from THC, CBD influences the endocannabinoid system indirectly, influencing the activity of several different neurotransmitters, including serotonin; this activity is thought to counteract the effects of THC, reducing negative effects such as anxiety.⁹ 

How cannabis use affects serotonin levels 

As mentioned above, serotonin is a neurotransmitter (chemical messenger) that carries out an important role in the body by regulating things such as mood, memory and anxiety.⁴ However, this role is only carried out successfully when the levels of serotonin present in the body are balanced. Certain cannabinoids, such as THC and CBD, can influence serotonin levels and how it works, as both these chemicals influence the uptake and release of serotonin. 

Impact of THC on serotonin

The impact THC has on the levels of serotonin in the brain is complex, and highly dependent on both the frequency of use and the dosage. THC has the ability to activate serotonin receptors, known as 5-HT receptors, as well as inhibit serotonin reuptake.¹⁰ A reduction of serotonin in the brain can lead to depression, which is why antidepressant drugs typically work by increasing the levels of serotonin in the brain. 

Recent studies have shown that cannabis, in low doses, can have a similar effect on the levels of serotonin in the brain by increasing these, highlighting its potential antidepressant effects.¹¹ The potential antidepressant effects occur because THC interacts and acts on cannabinoid CB1 receptors in the brain, which have a direct effect on the production and release of serotonin. The increased levels of serotonin can lead to higher feelings of wellbeing and enhanced moods.

However, when higher doses are taken or the drug is used chronically, it can have a negative effect on an individual and their serotonin levels. Chronic use can inhibit serotonin levels, causing both anxiety and depression, as the serotonin signalling becomes altered.¹² In addition, cannabis abuse in high concentrations can end up mimicking serotonin syndrome, a potentially life threatening drug reaction caused by too much serotonin.¹² 

Symptoms of this syndrome include:

• Vomiting
• Tremors
• Sweating
• High blood pressure
• Delirium (confusion)
• Seizures

CBD’s influence on serotonin

CBD interacts with 5-TH serotonin receptors, having both analgesic (pain relief) and anxiolytic (anxiety reducing) effects, further highlighting CBD’s therapeutic potential for treating conditions such as psychosis, chronic pain, and anxiety.¹³ 

Unlike THC, CBD does not increase the levels of serotonin released, however, CBD influences serotonin levels by interacting with serotonin receptors, acting as an allosteric modulator, which are substances that bind to a receptor changing its response to stimuli. In particular, it interacts with the 5-HT1A receptor associated with mood regulation, stress, and anxiety. The interaction between CBD and 5-HT1A receptors has a similar effect to selective serotonin reuptake inhibitors (SSRIs), increasing the availability of serotonin in the brain, helping to treat both anxiety and depression. 

Clinical implications and limitations

As with many types of drugs, cannabis presents a series of different clinical implications and limitations, which include:¹⁵

• Benefits of cannabis for mental health include the possibility that CBD could be used as an alternative treatment for anxiety and depression
• Long-term cannabis use can lead to cardiovascular and respiratory risks
• CBD can have negative effects on mental health, if high doses are taken with high frequency, which can lead to increased anxiety and mood disorders

Summary

Cannabis is a plant-based drug obtained from the leaves, stems, and flowers of the Cannabis sativa plant. Cannabis has intricate interactions with serotonin, a neurotransmitter (chemical messenger) involved in mood regulation, behaviour, anxiety, and depression. 

There are two main types of cannabinoids found in cannabis, which include THC and CBD. When low doses of THC are used, which is the psychoactive component in cannabis, it can temporarily boost serotonin levels in the brain. THC offers mild antidepressant effects by activating serotonin receptors and inhibiting its reuptake. However, high doses or chronic use can have the opposite effect, decreasing serotonin levels, which could lead to anxiety and depression. In addition to this, high THC exposure could mimic serotonin syndrome in more severe cases. 

Differently to THC, CBD is a non-psychoactive compound that interacts indirectly with serotonin receptors, especially 5-HT1A, which is thought to help reduce anxiety. CBD does not increase serotonin directly but modulates receptor response, offering therapeutic effects. Overall, this article highlights both the potential advantages, together with the risks of cannabis consumption.