Which cannabinoids produce a psychoactive effect?

The psychoactive effect of cannabis is primarily attributed to specific cannabinoids present in the plant. These cannabinoids interact with the body's endocannabinoid system, producing various effects on mood, perception and cognition.

Key takeaways

• Delta-9-tetrahydrocannabinol (THC) is the main psychoactive cannabinoid found in cannabis.
• Cannabidiol (CBD) is non-psychoactive and has been proposed to moderate THC’s psychoactive effects, but clinical findings are mixed.
• Cannabinol (CBN) is often described as sedating, but clinical evidence for this is limited.
• Tetrahydrocannabivarin (THCV) interacts with the CB1 receptor in a dose-dependent way, and its effects in people are not well established.
• Other cannabinoids, such as cannabigerol (CBG) and cannabichromene (CBC), are believed to be non-psychoactive.

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Understanding the role of these cannabinoids is essential for understanding the psychoactive effects of cannabis and its potential therapeutic applications.

Delta-9-tetrahydrocannabinol (THC)

Delta-9-tetrahydrocannabinol, commonly known as THC, is the primary psychoactive cannabinoid found in cannabis. It is responsible for the euphoric and intoxicating effects often associated with marijuana use.

THC works by binding to the CB1 receptors in the brain, altering neurotransmitter release and affecting various cognitive and physiological processes.

THC is known to induce feelings of relaxation, joy and altered perception of time. It can also cause short-term memory impairment, coordination difficulties and increased appetite, commonly referred to as “the munchies”. THC’s effects on pain perception and on nausea and vomiting have also been studied, and a synthetic form of THC, dronabinol, is the active ingredient in a prescription medicine approved in the US.

It is important to note that THC levels can vary significantly between different strains of cannabis and even within the same strain, depending on factors such as cultivation methods and plant maturity. This variability in THC content contributes to the range of psychoactive effects experienced by individuals using cannabis.

THC’s effect on the body

When THC enters the body, it is rapidly absorbed into the bloodstream and distributed throughout various organs, including the brain. Once in the brain, THC binds to CB1 receptors, primarily found in areas responsible for mood, memory and perception. This interaction leads to the psychoactive effects associated with THC use.

THC’s psychoactive effects can vary depending on the dose used, the method of use, such as smoking, vaping or edibles, and individual factors such as tolerance and metabolism. While low doses of THC may induce mild euphoria and relaxation, higher doses can result in more intense psychoactive effects, including altered sensory perception and hallucinations.

Overall, THC plays a crucial role in the psychoactive effects of cannabis. However, it is important to note that cannabis contains various other cannabinoids, each with its own unique properties and potential effects on the body. Understanding the different cannabinoids and their effects can help individuals make informed decisions about cannabis use.

What is THC?

Cannabidiol (CBD) and its proposed anti-psychoactive effect

Cannabidiol, also referred to as CBD, has been proposed to have an anti-psychoactive effect that could moderate some of the psychoactive effects of THC. While THC is known for its ability to produce a euphoric high, CBD does not produce one and acts on the brain’s receptors differently from THC. Researchers have investigated whether this could reduce the intensity of THC’s psychoactive effects, but the results have been mixed.

Laboratory studies suggest that CBD does not activate the CB1 receptor, which is responsible for the psychoactive effects of THC, but can reduce its activation by other compounds, for example by acting as a negative allosteric modulator. Whether this lessens THC’s high in people is less clear: a randomised, double-blind trial in 46 healthy, infrequent cannabis users found no evidence that adding up to three times as much CBD as THC to vaporised cannabis reduced THC’s effects on memory, psychotic symptoms or other measures. Because CBD does not produce a high, it is popular with people who want to avoid THC’s psychoactive effects.

Furthermore, CBD interacts with the endocannabinoid system, which plays a role in regulating various physiological processes. Researchers have examined whether CBD could be relevant to anxiety and related conditions: a 2015 review reported that preclinical studies and short-term human experiments pointed to possible anxiety-reducing effects, but human evidence was limited to single doses with few studies in clinical populations, and efficacy has not been established.

What is CBD?

It is important to note that CBD does not cancel out the psychoactive effects of THC, and studies disagree on whether it reduces them at all. The specific effects of CBD may vary depending on factors such as dosage, individual biology and the ratio of CBD to THC in a particular cannabis product. It is always recommended to consult a healthcare professional before using CBD.

• Cannabidiol (CBD) is believed to have an anti-psychoactive effect.
• Studies disagree on whether CBD reduces the psychoactive effects of THC.
• Laboratory studies suggest it can reduce CB1 receptor activation.
• CBD interacts with the endocannabinoid system.
• Individual factors can affect the specific effects of CBD.
• Consult with a healthcare professional before using CBD.

Cannabinol (CBN) and its reported sedating effect

Cannabinol, known as CBN, is a cannabinoid that is often described as calming and sedating. However, earlier laboratory research has described CBN as non-psychoactive, and a 2021 review found that most available human studies did not show CBN producing cannabis-like effects. While THC is the main psychoactive cannabinoid found in cannabis, claims that CBN adds to the plant’s relaxing properties have not been confirmed. CBN is formed when THC is exposed to air and undergoes oxidation.

CBN is often marketed for sleep, but the evidence is limited. A 2021 review of published human studies found no clinical trials that had measured CBN’s effects with validated sleep questionnaires or overnight sleep monitoring, and concluded that there was insufficient evidence to support sleep-related claims. Since then, a small randomised, placebo-controlled crossover trial in 20 adults with insomnia disorder found that single doses of CBN did not significantly change time spent awake after falling asleep, its main outcome, although the higher dose was associated with changes in some secondary measures, such as self-rated sleep quality; the authors called for larger, longer trials. CBN is believed to interact with the body's endocannabinoid system, which regulates various functions, including sleep-wake cycles, but how this might affect sleep in people is not yet understood.

What is CBN?

To fully understand CBN’s reported sedating effect, it is important to consider its interaction with other cannabinoids. CBD, for example, has been proposed to moderate some of the psychoactive properties of THC, although clinical findings are mixed. Whether combining CBN with CBD may enhance calming or relaxing effects has not been established in clinical research, and research on CBN in general remains very limited.

In addition to CBN, other cannabinoids such as cannabigerol (CBG) and cannabichromene (CBC) are believed to be non-psychoactive. While these cannabinoids may not contribute to the psychoactive experience, they are being investigated, mostly in laboratory and animal studies, for possible anti-inflammatory and neuroprotective properties, and relatively little research has been carried out in people.

In summary

• CBN, a cannabinoid found in cannabis, is often described as calming and sedating, but clinical evidence for this is limited.
• Evidence that CBN improves sleep is limited and inconsistent.
• There is no clinical evidence that combining CBN with CBD enhances any sedating effect.
• Other cannabinoids such as CBG and CBC are considered non-psychoactive.

Tetrahydrocannabivarin (THCV) and its distinct effects

Tetrahydrocannabivarin, or THCV, is a cannabinoid that interacts with the CB1 receptor in a dose-dependent way. In laboratory and animal studies, it blocks the CB1 receptor at lower doses and may activate it at higher doses. Unlike THC, which is known for its intoxicating properties, THCV is often described as uplifting or stimulating, but these effects have not been established in controlled human studies.

THCV has a different molecular structure compared to THC, allowing it to interact with the CB1 receptor in a distinct way. A 2020 commentary in the Journal of Cannabis Research described a lack of psychoactive effects as THCV’s main difference from THC, and in a small pilot trial of 10 healthy men, THCV was subjectively indistinguishable from placebo and made some effects of THC weaker while increasing others. Claims that THCV increases focus and energy have not been confirmed in controlled studies, but its distinct profile has made it a sought-after compound for those looking for an alternative to THC.

THCV is also being studied for other possible effects. In rodent studies it reduced appetite and increased energy metabolism, and a small randomised, placebo-controlled pilot trial in 62 adults with type 2 diabetes, split across five study groups, reported lower fasting blood glucose with THCV than with placebo. Evidence on weight in people is limited. These findings are discussed in the same commentary, and laboratory studies have looked at THCV’s effects on bone marrow cells, but there is little evidence on effects such as anxiety or bone health in people, and more studies are needed.

It is important to note that THCV is found in relatively low concentrations in most cannabis strains, making it less common than THC or CBD. However, breeders and researchers are actively working to develop strains that are rich in THCV to meet the growing demand for this unique cannabinoid.