Summary: Researchers report CBD, a non-psychoactive compound in cannabis, can help protect against the psychiatric risks associated with THC.
Source: Indiana University.
IU neuroscientists find cannabidiol reduces symptoms such as impaired memory in adolescent mice simultaneously exposed to THC.
A study reported Sept. 5 by neuroscientists at Indiana University finds that a non-psychoactive compound in cannabis called cannabidiol, or CBD, appears to protect against the long-term negative psychiatric effects of THC, the primary psychoactive ingredient in cannabis.
Other research has shown that long-term use of cannabis increases adolescent drug users’ risk for certain psychiatric and neurological disorders, such as schizophrenia. The risk to teens is greater than ever since selective breeding of plants to produce higher levels of THC over the past several decades has substantially increased exposure to the compound.
“This study confirms in an animal model that high-THC cannabis use by adolescents may have long-lasting behavioral effects,” said lead author Dr. Ken Mackie, professor in the IU College of Arts and Sciences’ Department of Psychological and Brain Sciences and director of the Linda and Jack Gill Center for Biomolecular Science at IU Bloomington. “It also suggests that strains of cannabis with similar levels of CBD and THC would pose significantly less long-term risk due to CBD’s protective effect against THC.”
THC, or tetrahydrocannabinol, is the chemical in cannabis that causes the “high” experienced during its use. Cannabis with higher levels of THC possess lower levels of the protective CBD, and vice versa, due to a biological link between THC and CBD production in the plant. An analysis of cannabis seized by the U.S. Drug Enforcement Administration found that while THC levels rose 300 percent from 1995 to 2014, the levels of CBD have declined 60 percent.
In contrast to THC, CBD does not cause a “high.” It is also an important ingredient in medical cannabis. For example, CBD appears useful as a treatment for some forms of severe childhood epilepsy, and its use for severe epilepsy was approved by the Indiana legislature this year.
“This is the first study in a rigorously controlled animal model to find that CBD appears to protect the brain against the negative effects of chronic THC,” Mackie said. “This is especially important since heavy use of cannabis with higher levels of THC poses a serious risk to adolescents.”
To conduct their study, IU researchers divided adolescent or adult male mice into five groups. Three groups received 3 milligrams per kilogram of body weight of either THC, CBD, or THC with CBD every day for three weeks. The other two groups received a placebo or no treatment.
All mice were then tested for signs of impaired memory, obsessive-compulsive behaviors and anxiety immediately following treatment as well as six weeks after treatment.
The mice exposed to THC alone showed signs of impaired memory and increased obsessive-compulsive behavior immediately after treatment. The adolescent group still experienced these changes six weeks after treatment, whereas the adult group did not. Both groups experienced a long-term increase in anxiety.
By contrast, adult and adolescent mice exposed to CBD alone showed no behavioral changes immediately or six weeks after treatment. Most significantly, mice in both age groups that received CBD with THC exhibited no short- or long-term behavioral changes. These results suggest that long-term use of cannabis strains containing similar amounts of CBD and THC may be less harmful than long-term use of high-THC strains.
The first author on the IU study is Michelle Murphy, a Ph.D. student in the IU Bloomington Program in Neuroscience and Department of Counseling and Educational Psychology in the IU School of Education. Additional authors are associate professor Heather Bradshaw and research scientist Jim Wager-Miller in the Department of Psychological and Brain Sciences and in the Gill Center for Biomolecular Science and Program in Neuroscience; Emma Leishman, Ph.D. student in the Program for Neuroscience; and Joanna Winstone and Sierra Mills, undergraduate students in the Department of Psychological and Brain Sciences.
Funding: This research was supported by the National Institutes of Health’s National Institute on Drug Abuse.
Source: Kevin D. Fryling – Indiana University
Image Source: NeuroscienceNews.com image is credited to Ben Mills.
Original Research: Full open access research for “Chronic Adolescent Δ9-Tetrahydrocannabinol Treatment of Male Mice Leads to Long-Term Cognitive and Behavioral Dysfunction, Which Are Prevented by Concurrent Cannabidiol Treatment” by Murphy Michelle, Mills Sierra, Winstone Joanna, Leishman Emma, Wager-Miller Jim, Bradshaw Heather, and Mackie Ken in Cannabis and Cannabinoid Research. Published online September 1 2017 doi:10.1089/can.2017.0034
Chronic Adolescent Δ9-Tetrahydrocannabinol Treatment of Male Mice Leads to Long-Term Cognitive and Behavioral Dysfunction, Which Are Prevented by Concurrent Cannabidiol Treatment
Introduction: The high prevalence of adolescent cannabis use, the association between this use and later psychiatric disease, and increased access to high-potency cannabis highlight the need for a better understanding of the long-term effects of adolescent cannabis use on cognitive and behavioral outcomes. Furthermore, increasing Δ9-tetrahydrocannabinol (THC) in high-potency cannabis is accompanied by a decrease in cannabidiol (CBD), thus an understanding of the interactions between CBD and THC in the neurodevelopmental effects of THC is also important. The current study examined the immediate and long-term behavioral consequences of THC, CBD, and their combination in a mouse model of adolescent cannabis use.
Materials and Methods: Male CD1 mice received daily injections of THC (3 mg/kg), CBD (3 mg/kg), CBD+THC (3 mg/kg each), vehicle, or remained undisturbed in their home cage (no handling/injections), either during adolescence (postnatal day [PND] 28–48) or during early adulthood (PND 69–89). Animals were then evaluated with a battery of behavioral tests 1 day after drug treatment, and again after 42 drug-free days. The tests included the following: open field (day 1), novel object recognition (NOR; day 2), marble burying (day 3), elevated plus maze (EPM; day 4), and Nestlet shredding (day 5).
Results: Chronic administration of THC during adolescence led to immediate and long-term impairments in object recognition/working memory, as measured by the NOR task. In contrast, adult administration of THC caused immediate, but not long term, impairment of object/working memory. Adolescent chronic exposure to THC increased repetitive and compulsive-like behaviors, as measured by the Nestlet shredding task. Chronic administration of THC, either during adolescence or during adulthood, led to a delayed increase in anxiety as measured by the EPM. All THC-induced behavioral abnormalities were prevented by the coadministration of CBD+THC, whereas CBD alone did not influence behavioral outcomes.
Conclusion: These data suggest that chronic exposure to THC during adolescence leads to some of the behavioral abnormalities common in schizophrenia. Interestingly, CBD appeared to antagonize all THC-induced behavioral abnormalities. These findings support the hypothesis that adolescent THC use can impart long-term behavioral deficits; however, cotreatment with CBD prevents these deficits.
“Chronic Adolescent Δ9-Tetrahydrocannabinol Treatment of Male Mice Leads to Long-Term Cognitive and Behavioral Dysfunction, Which Are Prevented by Concurrent Cannabidiol Treatment” by Murphy Michelle, Mills Sierra, Winstone Joanna, Leishman Emma, Wager-Miller Jim, Bradshaw Heather, and Mackie Ken in Cannabis and Cannabinoid Research. Published online September 1 2017 doi:10.1089/can.2017.0034