Dr. Michael Taffe: Development of an e-Cigarette Model for the Study of Cannabinoid Vaping in Rats
By Lais F. Berro, Ph.D., Animals in Research Committee Member
Vaping devices, also known as e-cigarettes, have become increasingly popular, particularly among teenagers. Although initially promoted for cigarette smokers, the e-cigarette technology has also markedly changed marijuana use. Millions of people now vape cannabis and cannabis extracts, with epidemiological studies showing that nearly 10% of teenagers report having vaped cannabis in the past year. Many cannabis e-cigarette users report vaping ∆9‐tetrahydrocannabinol (THC), the ingredient in marijuana that makes people feel “high”. However, the vaping of cannabidiol (CBD), another ingredient of marijuana, has also increased in recent years due to the claimed health benefits of this compound. Anecdotal and empirical evidence suggests that CBD use can improve mood, sleep, anxiety, pain, and even acne.
Despite the recent and growing trends in THC and CBD vaping, not enough research has been done to understand the benefits and risks of this form of cannabis use. This gap in scientific knowledge exists not only because the vaping technology is still relatively new, but also due to federal rules that limit research into the effects of cannabis in humans. Therefore, this knowledge gap can only be filled by the employment of animal models. But how to model vaping in animal subjects?
Dr. Michael Taffe and his research team at The Scripps Research Institute (the Taffe Laboratory is now at the University of California-San Diego) were up to the task. In the last 5 years, the Taffe laboratory has developed and validated a method for delivering THC and CBD (among other drugs of abuse) to rats using commercial e-cigarette technology. Using this model, which consists of placing the rats in a sealed chamber that regulates airflow and the delivery of vaporized drug using e-cigarette devices, Dr. Taffe and his group have investigated many health and behavioral effects of CBD and THC vaping.
Among these findings, studies from Dr. Taffe’s laboratory have shown that THC, but not CBD, inhalation decreased pain sensitivity in rats. These studies point to THC as the main cannabis constituent responsible for its pain-decreasing effects and show that CBD may not be effective for some kinds of pain. Importantly, they also showed that the effects of THC vaping on pain sensitivity were reduced with repeated daily THC inhalation, an effect called “tolerance”. Female rats were more likely to develop tolerance than males. Therefore, repeated THC vaping could make its beneficial effects on pain less robust over time, especially in women.
Given the increasing popularity of cannabis extract vaping among teenagers, Dr. Taffe and his team have also set out to investigate the consequences of adolescent THC vaping using their new rat e-cigarette model. They have shown that repeated THC vaping in adolescent rats has lasting consequences into adulthood. After repeated THC vaping as adolescents, adult male rats consume more food, and adult female rats have reduced pain-decreasing effects in response to THC. A particularly alarming finding from this research was that adolescent THC vaping increased the abuse potential of the opioid drug fentanyl in adult female rats.
Opioid drugs are potent pain relievers, but because they also produce euphoria, opioid misuse and abuse has increased dramatically in the United States. The US opioid crisis has led to increased restrictions on prescription opioids, with a consequence being the urgent need for alternative pain killers. As an increasing numbers of patients turn to medicinal cannabis to fight pain, they also have used it to enhance the effects of opioid analgesics. Unfortunately, little is known about the safety of this combination. Using their rat “vaping chambers”, Dr. Taffe’s group has looked at whether THC vaping can alter how much adult male rats take of the prescription opioid oxycodone (OxyContin®) in a rat abuse model. Their results were very encouraging: THC vaping not only decreased the intake of oxycodone, but it also potentiated its pain-decreasing effects. Together, these data supported the potential use of THC to enhance the therapeutic efficacy, and to reduce the abuse, of prescription opioids. Going back to their study in adolescent rats, however, the same effects were not observed when THC vaping happened during adolescence. Instead, adolescent THC vaping only increased the intake of the opioid fentanyl in female rats when studied as adults. Therefore, THC vaping during adolescence seems to be particularly dangerous, a critical finding in light of the large number of teenagers who now vape cannabis and cannabis extracts.
The work of Dr. Michael Taffe has shed light into many health effects of THC and CBD, both positive and negative. His work in adolescent rats has also highlighted the importance of raising awareness about the potentially dangerous and long-lasting consequences of cannabis extract vaping among teenagers. The establishment of a highly translational rodent e-cigarette model represents a major advancement in cannabinoid science. As recent reports of problems associated with THC vaping increase among human users, Dr. Taffe’s research is at the forefront of investigating the therapeutic and deleterious effects of cannabinoid vaping. We look forward to learning about his future contributions to the field.
Michael A. Taffe, Ph.D., has been a member of CPDD since 1998 and has served on the Publications and Media committees. Lais F. Berro, Ph.D., has been a member of CPDD since 2018 and currently serves on the Animals in Research committee.