Women and Weed: Findings from Formerly Forbidden Research, Part 1

Part 1. Differences in Men and Women and Weed

 Current legal status U.S.

First banned for use in the 1937 Marijuana Tax Act, cannabis remains under the regulation of the Drug Enforcement Agency (DEA) under Schedule I of the Controlled Substance Act of 1970 (with amendments through 2017). Drugs under Schedule I, by definition have a high potential for abuse and have no accepted medical use. However, some cannabis derivatives have been found to be therapeutic. Marinol (pure tetrahydrocannabidiol (THC) and dronabinol (synthetic THC) have been FDA approved to treat nausea and vomiting induced by chemotherapy and are listed in Schedule III. Pure cannabidiol (CBD; Epidiolex) is listed as a Schedule V substance and is used to control epilepsy caused by a rare pediatric seizure disorder. Other CBD extracts remain under Schedule I.

Because cannabis remained illegal in the U.S. until very recently, medical researcher’s ability to study the effects of THC on the body has been limited. Now that the plant has been legalized for medicinal and/or recreational use in many states, research into the effects, and potential therapeutic uses, of THC and other cannabinoids has escalated. One study published in the journal of the American Medical Association in 2014 found that states with medical marijuana laws had lower opiate overdose deaths by an average of 25%. On the other hand, recent findings of a fetal-alcohol-like birth defect has been reported in fetuses exposed to cannabinoids in-utero. Obviously, research needs to continue.

How does cannabis work in the body?

There are hundreds of chemical components, called cannabinoids, in the marijuana or cannabis plant. The one that is most obviously active, because it is psychoactive, is THC (delta-9-tetrahydrocannabinol), first identified in the cannabis plant in the 1960s. CBD is another. It wasn’t until the late 1980 and 1990s, while studying cannabinoids, that scientists discovered an entire signaling system, which they named the endocannabinoid (EC) system, that is responsible for mammalian biological homeostasis or balance.

Receptors in the endocannabinoid system respond to cannabinoid molecules that

1) are naturally made by the body (endogenous),

2) are ingested from a cannabis plant, or

3) are made in a lab (synthetic cannabinoids).

The human body has complex communication systems that send chemical messages from the brain to other areas of the body, and vice versa, along nerve pathways. The messages travel like trains back and forth from the central station in the brain along these pathways jumping from one nerve ending to another at specific junctions called synapses. The nerve junctions are spaces where chemical signals jump from the sending end of one nerve to the receiving end of the next nerve along a chain of pathways until the message reaches its intended destination station. Receptors on the receiving nerves have to fit perfectly with the chemical signal from the preceding nerves for the message to keep moving along the right pathways to get delivered to the right cells in the right places.

Smoking, vaping, or ingesting cannabis releases high amounts of cannabinoid chemicals into the system. By binding to the receptors in the nerves, the endogenous cannabinoids are blocked which interferes with the normal balance of the EC system. The overwhelmed chemical messaging system gets bogged down, the messages slow down, and a person feels “stoned.” It’s a train wreck!

Cannabinoid receptors are found in many areas of the brain. Therefore, THC would have an effect on many brain functions. For example:

This part of brain:	Regulates:	THC might cause:
Amygdala	fears and anxiety	paranoia
Hippocampus	learning	impaired memory
Nucleus accumbens	rewards	euphoria
Hypothalamus	eating	increased appetite
Spinal cord	conducting pain signals	altered sensation or pain
Neo cortex	complex thinking	altered judgment

The location of cannabinoid receptors is not limited to the brain; they are also found on nerves throughout the body. CBD is a cannabinoid created endogenously or ingested. While similar in structure to THC, CBD is not psychotropic or intoxicating and is only minimally active in the brain. THC binds most specifically with CB1 receptors in the brain and CBD binds more specifically with CB2 receptors throughout the body – particularly with the CB2 receptors in the immune and gastrointestinal system. That helps explain THC’s predominantly psychotropic effects and CBD’s major benefits in chronic pain syndrome relief and inflammatory bowel syndromes. The density and balance of cannabinoid receptors vary from person-to-person, which is why one person will get a happy high and another will be predominately paranoid after smoking the same amount of weed.

 Differences in cannabis use and response between women and men

Cannabis use in women has greatly increased over the past five to ten years. In women between the ages of 18 to 25, the overall use of weed increase by 20%, daily use rose 13%, and the reported incidence of cannabis use disorder (CUB) increased by 30%. In women over the age of 26, both monthly use and daily use increased by 40%.

While a higher percentage of women report using weed for medical purposes, more men are registered for medicinal use across the U.S.

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Women and weed:

Lower numbers of women use weed and they tend to start using it later in life

More likely to prefer oral ingestion over other forms of intake

Different responses at different times and with different cannabis strains, likely due to levels of estrogen (more sensitive to THC with high estrogen levels (e.g, at ovulation) less sensitive to THC effects when have low estrogen levels (e.g., at menses)

Higher rates of use for medicinal reasons like pain and anxiety, and to help cope with social and psychological stress; dysmenorrhea, PMS, nausea, bloating, headaches

Higher number and density of CBD receptors in brain and body; probably why women need a lower dose of THC to get same degree of intoxication

More likely than men to get anxiety-related symptoms from occasional use

CBD causes a markedly steeper decrease in anxiety in women than in men; THC at low doses relieved anxiety and at high doses increased anxiety, CBD showed no difference by dose.

THC more effective than CBD in relieving centralized pain in women

THC more effective for improving quality of life, anxiety, and depression in women than in men

Higher side effects of THC – anxiety, paranoia, dizziness, disorientation (difficulty navigating especially through unfamiliar areas, locating items, feeling off-balance), especially at higher doses

Increase in hunger about 3 hours after ingestion*

At smaller doses, increases sexual appetite in women (high doses decrease this effect)

Chronic use may negatively affect women’s memory and emotional processing centers.

Less likely to develop CUD, but shorter time progression to CUD; have more difficulty stopping use and relapse is more likely; in CUD, have more anxiety disorders and panic attacks.

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Men and Weed:

Higher rates of use by men (3/4 of all users are men); men start at an earlier age than women and have more access to drugs in general

More likely to smoke or vape over edibles

More stable reaction to THC (consistent reaction to specific strains)

Male hormones are affected – THC blocks production of gonadotropins in the pituitary gland and elsewhere, depressing the production of testosterone and other hormones, and interfering with prostate function and sperm production

Higher rates of use for recreational purposes (about 62% of recreational users were male)

More likely to be using other substances as well

THC and CBD do little to decrease in anxiety in men and CBD may increase anxiety

THC more effective at relieving peripheral pain in men than in women

Experience increased appetite immediately upon smoking THC*

Causes decreased sexual appetite and sperm production

Results in higher rates of cannabis use disorder (CUD) and more severe symptoms

Take longer to build up tolerance to weed and develop CUD than women

*Animal testing found that THC increased the consumption of sweetened condensed milk by male rats in the first through third hour after injection, but didn’t increase consumption by female rats until the third hour after injection. Similar responses were seen in guinea pigs.

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Studies show that cannabis affects men and women differently, for several reasons. One is that men and women start out differently. Women are more likely to struggle with pain, sleep deprivation, anxiety, and depression. Because of all those cannabinoid receptors in the brain, THC affects issues that start in the “head” like anxiety and pain:

Anxiety: THC and CBD both reduced anxiety levels in studies of men and women. But women showed a steeper decrease in anxiety than did men after smoking weed. Women started out with higher anxiety levels and ended up with lower anxiety levels than men. But there is a cautionary note. Low doses of THC worked better to reduce anxiety than higher doses. At higher doses, anxiety increased.

CBD, on the other hand, also decreased anxiety in women and had no dose effect; no danger of taking too much and worsening the anxiety. Men, however, saw no decrease in their anxiety with the use of CBD – in fact, they experienced higher levels of anxiety. These findings are similar to the results of CBD testing in anxious mice as well. In a paradoxical twist, CBD can reduce anxiety induced by THC, though no human studies have been done to test this.

Pain: Interestingly, pain is perceived and experienced differently by men and women whether we are talking about acute pain or chronic pain. Women have much higher sensitivity to external stimuli in the environment and more internal pain throughout the body. Some scientists think it is due to estrogen, some think there may be more pain receptors in their brains. Because of this increased sensitivity, women have higher rates of chronic pain conditions.

Recent studies suggest that men and women respond differently to types of pain. Men are more sensitive to inflammatory pain, like arthritis, or knee injury, or tooth ache. Women are more sensitive to nerve pain and centralized pain, like sciatica, migraines, stomach pain. Successfully treating different types of pain may depend on whether the patient is biologically male or female. For example, women get more pain relief from opioids than men do but they also experience more side effects. Therefore, women might feel better on a lower dose. Studies on cannabinoids have found that CBD is more effective at relieving peripheral and inflammatory pain (the kind of pain that men are more sensitive to) and THC works better against nerve and centralized pain (the kind that more women suffer from).

Women experience about twice as much chronic pain as men and experience more pain during the pre-menstrual phase of the menstrual cycle when their estrogen levels are high. Because pain cues come from the brain, and women have more cannabinoid receptors in the brain, tricyclic and SNRI antidepressants and cannabinoids can be effective at treating their pain.

If seeking pain relief, trying CBD first is the safer option as it is lower in unwanted side effects than THC. However, adding a low dose of THC (low dose THC works better for pain than high doses) may help if pain is not relieved by CBD alone.

Map Source: https://disa.com/map-of-marijuana-legality-by-state

Coming up soon:
Women and Weed: Findings from Formerly Forbidden Research
Part 2 – Pregnancy, Breastfeeding, and Insomnia