THC-Induced Hypothermia: Mechanisms and Findings

Tetrahydrocannabinol (THC), the primary psychoactive component of cannabis, affects mood, perception, and appetite. Research also indicates its impact on body temperature regulation, with some studies showing that THC can cause hypothermia—a drop in core body temperature. This response is linked to interactions with the endocannabinoid system, though the precise mechanisms remain under investigation.

Understanding THC’s influence on thermoregulation provides insight into its physiological effects and potential therapeutic applications or risks.

Physiological Basis Of Body Temperature Regulation

The body maintains a stable internal temperature through neural, hormonal, and vascular mechanisms. Thermoregulation is primarily controlled by the hypothalamus, which acts as a central thermostat. Sensory inputs from thermoreceptors in the skin and deep tissues relay temperature changes to the hypothalamus, triggering physiological responses to conserve or dissipate heat. When external temperatures rise, vasodilation increases blood flow to the skin, promoting heat loss through radiation and evaporation. In colder conditions, vasoconstriction reduces heat dissipation, while shivering generates heat through muscle contractions.

Endocrine signaling also plays a role in temperature regulation. Thyroid hormones, particularly thyroxine (T4) and triiodothyronine (T3), influence basal metabolic rate and heat production. Catecholamines such as epinephrine and norepinephrine stimulate brown adipose tissue, generating heat through mitochondrial uncoupling. This process, known as non-shivering thermogenesis, is especially significant in neonates and individuals exposed to prolonged cold.

Neurotransmitters further contribute to thermoregulation. Serotonin influences heat dissipation, while dopamine affects thermoregulatory set points. Endogenous opioid peptides modulate thermal perception, particularly during stress-induced temperature fluctuations. These interactions highlight the balance between central and peripheral mechanisms in maintaining thermal stability.

Role Of Endocannabinoid Receptors

The endocannabinoid system (ECS) modulates various physiological processes, including thermoregulation. This system consists of endogenous ligands, receptors, and enzymatic pathways that regulate their synthesis and degradation. Cannabinoid receptor type 1 (CB1) is particularly relevant to temperature control due to its high expression in the central nervous system, including the hypothalamus. Activation of CB1 receptors affects neuronal excitability and neurotransmitter release, influencing the body’s ability to maintain thermal homeostasis.

Endocannabinoids such as anandamide (AEA) and 2-arachidonoylglycerol (2-AG) bind to CB1 receptors, modulating synaptic activity in brain regions involved in temperature control. Studies show that CB1 activation in the preoptic area of the hypothalamus alters heat dissipation and retention. Increased CB1 signaling suppresses excitatory neurotransmission in this region, reducing metabolic heat production and lowering core temperature. Rodent studies confirm that CB1 receptor agonists induce hypothermia, an effect reversed by CB1 antagonists.

Peripheral mechanisms also contribute to the temperature-lowering effects of CB1 activation. CB1 receptors in brown adipose tissue suppress non-shivering thermogenesis by inhibiting sympathetic nervous system activity, reducing mitochondrial uncoupling protein 1 (UCP1) expression and heat generation. Additionally, CB1 activation promotes vasodilation, facilitating heat dissipation. These findings demonstrate how endocannabinoid signaling influences multiple thermoregulatory pathways.

THC-Induced Thermal Alterations

THC consistently reduces core body temperature in a dose-dependent manner through its interaction with cannabinoid receptors. This effect begins shortly after administration and can last for several hours, varying based on dosage, method of consumption, and individual metabolism. Studies indicate that moderate to high doses produce the most pronounced hypothermic response, while lower doses yield minimal or inconsistent changes. This pattern aligns with THC’s biphasic effects, where different concentrations produce opposing physiological responses.

THC-induced hypothermia is linked to its modulation of neurotransmitter activity in thermoregulatory centers of the brain. THC suppresses excitatory neurotransmission in the preoptic area of the hypothalamus, shifting the body’s thermal set point downward. This suppression reduces metabolic heat production and sympathetic nervous system activity, decreasing thermogenesis in brown adipose tissue. Additionally, THC promotes vasodilation, increasing blood flow to the skin and enhancing heat dissipation.

Environmental conditions and physiological state influence THC’s hypothermic effects. In colder settings, the body may counteract temperature drops through shivering or hormonal adjustments. In warm environments, THC can exacerbate heat loss by further enhancing vasodilation. Individual differences in cannabinoid receptor expression and sensitivity also contribute to variability in thermoregulatory responses.

Animal Findings In Laboratory Studies

Controlled studies in rodents show that THC reliably induces hypothermia. Early research demonstrated that THC administration in rats and mice led to significant core temperature reductions within 30 to 60 minutes, lasting for several hours depending on dosage. More recent studies confirm a dose-dependent response, with moderate to high doses producing pronounced temperature decreases, while lower doses result in minimal effects.

Experiments using CB1 receptor antagonists confirm that CB1 activation is responsible for THC-induced hypothermia. When rodents are pretreated with CB1-specific antagonists such as SR141716A (rimonabant), the hypothermic response is significantly reduced or blocked. In contrast, CB2 receptor modulation has little effect on thermoregulation, as CB2-selective agonists do not produce similar temperature reductions, and CB2 antagonists fail to counteract THC-induced hypothermia.

Observations In Human Participants

While animal studies consistently demonstrate THC-induced hypothermia, human research presents a more complex picture. Human thermoregulation is influenced by metabolic rate, body composition, and environmental conditions, making responses more variable. Clinical studies indicate that THC can cause mild reductions in core body temperature, typically around 0.2–0.5°C (0.4–0.9°F), though the effect is often transient and varies based on dose and method of administration.

THC also affects thermal perception. Some users report sensations of coldness, even in neutral temperatures, which may be linked to THC’s influence on vasodilation and sensory processing. Functional imaging studies suggest that THC alters activity in brain regions involved in thermal perception, such as the insular cortex. However, unlike in animal models where the hypothermic response is more pronounced, human studies suggest that compensatory mechanisms, including behavioral adaptations and metabolic adjustments, help mitigate extreme temperature drops. This variability indicates that while THC influences thermoregulation in humans, its effects are less predictable than in controlled animal experiments.