CBD and human physiology

The way cannabidiol interacts with the human body is a complex biochemical cascade involving the endocannabinoid system, cannabinoid receptors, and metabolic effects. The endocannabinoid receptor members of the G-protein family coupled with a prominent presence in the central nervous systems, skeletal muscles, spleen, and the peripheral nerves. The distribution pattern of these receptors allows cannabinoids and CBD to modulate the body’s response in immunity, inflammation, mood, appetite, neurotransmission, brain reward circuitry, cognition, and sleep.     

Anandamide was the first endocannabinoid discovered and studied extensively in animal subjects. Pure isolates of this compound exhibited noticeable effects in animal subjects. Endocannabinoids in the human are rapidly destroyed, making their actions transient. The search for more stable forms of these compounds has led to the discovery of synthetic cannabinoids with improved activity and safety profile. Primarily, CBD works in humans by mimicking the actions of anandamide and other endocannabinoids. It binds to the cannabinoid receptors distributed in the body to influence the basic physiological flow of the human body.   


CBD effects and sex differences

There have been different reports and observations on variations in the effects of drugs noticed in men and women. The main biological point of difference suggested to be responsible for the slight response levels noticed in both genders is centered on genetic composition and hormonal behaviors. With regard to these differences, men and women are believed to process information differently, express emotions in a different manner, and display noticeable differences in attitude and social skills. Coupled with a difference in body organization and brain anatomy, drugs with effects on the central nervous system and peripheral nerves are expected to elicit variations in response patterns. 

As expected, different scientific explanations have been proposed to explain the response variable on a cellular level. In 1999, a research report on the expression of cannabinoid receptors and their gene transcription in human blood cells was published by the Journal of Progress in Neuro-Psychopharmacology & Biological Psychiatry. The study showed that the expression of the cannabinoid receptors is dependent on gender and ethnicities with higher levels of cannabinoid receptors subtype 1 (CB1) found in men. In other studies, the sex-dependent difference in humans in response to centrally acting drugs such as CBD has been linked to the modulatory effects of gonadal steroid hormones. Female rats in a high-estradiol state are more sensitive to the central effects of cannabinoids when compared with female rats not in the cycle.


Sex-dependent effects of cannabinoids in humans

The group of literature studying sex-dependent effects of cannabinoids in humans and animal subjects uses more units of cannabis or 9-delta-tetrahydrocannabinol. Most researchers studying this subject also use human subjects to extrapolate effect suggestions in humans. 


  • Analgesia

The pain-relieving property of cannabinoids was discovered many years ago; however, literature studying the sex-dependent response of animal subjects to cannabinoids only surfaced a short while ago. In 2016, a survey investigating the response rate of over 100 patients to medical cannabis for the treatment of rheumatic pain observed that over nearly half of this population were women. This survey agreed with an early report published in 2009, which revealed that about 40 percent of total patients treated with medical cannabis for chronic pain in Washington were women. Confirming these observations, a research study published by the Journal of Pharmacology and Experimental Therapeutics confirmed that the cannabinoid-induced anti-nociceptive effect is greater in female rats compared to male rats.  



  • Anxiety 

Cannabinoids are used as an alternative therapy method for the management of anxiety in patients with chronic health conditions. However, the effects noticed in these patients are somehow complicated as the effects of cannabinoids on anxiety-like behaviors appear to be dose-dependent. At high doses, anxiety attacks are more pronounced, and at low doses, cannabinoids exhibit anxiolytic effects. Research conducted to study the sex-related differences in anxiety treatment using cannabinoids suggests that females have a higher risk of pronounced anxiety-like behaviors. 

A report published by the Journal of Behavioral Brain Research provided evidence that the incidence of anxiety-like behaviors increases in female rats when exposed to a cannabinoid agonist when compared to male rats. This research ultimately provided partial evidence for different observations and survey evaluations reporting more anxiety-like behavior in females following the administration of a high dose of a cannabinoid. 


  • Energy homeostasis

As agonists of the endocannabinoid system, cannabinoids have long been known to play a pivotal role in the cellular mechanism regulating energy homeostasis. However, studies investigating the sex-dependent effects of cannabinoids on this function were not available until recently. A study with interest in this subject was performed in 2009 using gonadectomized guinea pigs and transgenic cannabinoid one receptor knockout mice. A microanalysis of feeding behavior on the test subjects revealed that male subjects were more sensitive to the hyperphagic and hyperphagic effects of both cannabinoid one receptor agonists and antagonists. The hyperthermic and hypothermic effects of these compounds were more pronounced in male subjects.


  • Acute effects 

Acute effects of cannabinoids are noticed within minutes after administration of a single dose. These effects include dizziness and transient bouts of euphoria. Currently, the evidence on sex-dependent variations of cannabinoids in relation to these effects is inconclusive and equivocal. However, many drug use surveys suggest that females report significantly more cases of acute effects of cannabinoids than males.


  • Catalepsy and locomotor effects

Unlike other effects as studied, the sex-dependent effect of cannabinoids on catalepsy and locomotor behaviors in rats appears to be definite and not equivocal. In 2004, a research report published by the Journal of Psychopharmacology suggested that cannabinoids elicit greater catalepsy and locomotor effects in females when compared with the males. 

In essence, the difference noticed in the properties of cannabis compounds in both males and females has been attributed to dissimilar hormonal composition and different levels of expression of the cannabinoid receptors. 



Ian Parkes

Ian has been writing for a number of high growth industries for the past decade. Having plied his trade in the craft beer industry, Ian drew parallels between that and the world of CBD and soon became fascinated. Ian enjoys writing about innovation in the industry, particularly as it relates to the development of the leading brands.

See all posts by Ian Parkes

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