How sex, hormones and adolescence play a role in THC’s effects

Estimated reading time: 5 minutes

Researchers at the University of Chicago have been exploring how cannabis – particularly THC – may affect certain demographics differently.

In response to the increasing use of cannabis globally, a team of researchers at the University of Chicago have set out to better understand how it may affect certain demographics.

As cannabis legalisation and access expands, they argue, it becomes increasingly crucial for people to understand it more fully.

Harriet de Wit, PhD, a professor in the Department of Psychiatry and Behavioral Neuroscience, is studying the effects of THC — the main psychoactive ingredient in cannabis — in specific groups of people.

Her research team recently released two papers on the effects of cannabis in women and adolescents. 

The studies measured real-time effects of THC in human participants in tightly controlled settings. 

They found that increasing doses of THC can increase bodily anxiety in women, and that compared to adults, adolescents are more negatively impacted by THC on cognitive tasks.

Gender and hormones may play a role in THC’s effects 

Historically, subjects in animal and human studies have been male, with researchers claiming that it is too difficult to control the fluctuating hormones in the female body. 

Yet this is why it is crucial to include women, to understand the differences and potential risks when hormones enter the picture. Many individuals also take hormones as birth control or to affirm gender identity. These external hormones could interact with medical treatments and drugs as well.

PhD candidate in the de Wit lab, Elisa Pabon, PhD, has published one of the first papers to examine the effects of THC specifically in women, as part of a larger study on the interaction of THC and the menstrual cycle. 

In animal studies, responses to THC differ between males and females, and THC sensitivity depends on the level of the female hormone estradiol. By studying women at a specific phase of the menstrual cycle, Pabon found that increasing doses of THC increases physical signs of anxiety.

Participants were given either a placebo, low THC, or high THC dose across three sessions. 

All participants were cisgender adult women with regular menstrual cycles and were, at the time of the sessions, in the follicular phase. This is the longest phase of the cycle and starts on the first day of a period and lasts until an egg is released.

To measure drug effects, Pabon used questionnaires and electrocardiogram (ECG) recordings of the heart and circulatory system. Together, they measured subjects’ physical and psychological levels of anxiety.

Larger THC doses were shown to increase heart rate and decrease heart rate variability, both indicators that physical anxiety increases in women due to greater THC. 

However, these measures were not actually associated with subjective feelings of anxiety. At the higher THC dose, subjects reported greater cannabis effects, but not anxiety effects.

“So much of what we believe is based on studies in males, a lot of knowledge may not hold true in females,” commented de Wit.

“Any drug can work in a variety of different ways. The receptors and pathways that account for the psychological effects to THC might differ from the physiological. The mechanisms might be dissociated.”

“It’s important for us to understand what variables influence responses to drugs.”

According to the researchers, it is too soon to rule out the impact of hormones altogether, as the subjects in Pabon’s study were in a specific phase of the menstrual cycle, and a direct comparison with male participants has yet to be made. 

However, these findings lay the groundwork for measuring physical and subjective drug effects side-by-side in different populations. 

Teens and the THC ‘trance’

The researchers have also been exploring whether adolescents are more negatively impacted by THC on cognitive tasks.

The study recruited adolescents (age 18-20) and adults (age 30-40) to take part in three sessions. In each session, subjects received a placebo, low THC dose (7.5 mg), or high THC dose (15 mg) orally. 

Subjects across groups were matched for several important factors, such as sex, weight, and tolerance to cannabis and data was collected in the form of EEG, a physical signature of cognition, performance on several cognitive behavioural tasks, and subjective answers to questionnaires. 

The electrodes in the EEG picked up brain waves, and different frequencies of waves are known to signify different types of cognitive processes. The alpha wave is a mid-range frequency that is strongest during relaxation and reduced sensory input, such as closing of the eyes.

THC had no detectable effect on brain waves at rest in either the adults or adolescents, but the differences in how THC affects the brain and cognition between the age groups became clear during task performance.

Specifically, when adolescents consumed THC, they were less capable than adults of exiting the alpha wave state during task engagement. 

The adolescents’ difficulty in exiting the THC trance was reflected in four other tasks, which required subjects to stay attentive, react rapidly — or stop themselves from reacting too rapidly, recall the recent past, and judge how much time has passed. 

Across tasks, adolescents performed more poorly than adults, and performance further declined when the THC dose was higher. 

While adolescents experienced significant negative effects on their cognitive performance, they did not differ from adults in their feelings about the drug’s subjective effects, stating similar feelings of like/dislike, awareness of intoxication, and mood state during the sessions.

While adolescents may not feel any more intoxicated by cannabis than adults, their behaviour could be more negatively impacted. 

Read the full study here 

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