Browsing by Subject "THC"

Now showing 1 - 7 of 7
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    Acute and long-term effects of Δ9-tetrahydrocannabinol on object recognition and anxiety-like activity are age- and strain-dependent in mice
    (Elsevier, 2017-12) Kasten, C.R.; Zhang, Y.; Boehm II, S.L.; Psychology, School of Science
    Use of exogenous cannabinoids disrupts the fine-tuned endocannabinoid receptor system, possibly leading to alterations in cognition, memory, and emotional processes that endure long after cannabinoid use has stopped. Long-term adolescent use may uniquely disrupt these behaviors when compared to adult use. The current study explored the acute and long-term behavioral effects of six 10mg/kg Δ9-tetrahydrocannabinol (THC) injections across the adolescent or early adult period in male inbred C57Bl/6J and DBA/2J mice. The acute and prolonged effects of THC on object memory using the novel object recognition task, unconditioned anxiety in the elevated plus maze and open field, and sedative effects in the open field were examined. Acute THC treatment resulted in anxiogenic activity in both strains, but only caused sedation in B6 mice. Repeated THC treatment resulted in a protracted effect on object recognition, but not unconditioned anxiety, assessed 4weeks later. In both strains, an adolescent history of THC treatment disrupted later object recognition. Interestingly, in B6 mice an adult history of THC exposure appeared to rescue a deficit in object recognition observed in vehicle-treated adults. Repeated THC administration also produced a protracted effected on CB1R protein expression. Animals treated with THC in adolescence maintained increased levels of CB1R protein expression compared to their adult THC-treated counterparts at five weeks following the last injection. These results indicate that THC use may have long-lasting effects with adolescence being a unique period of susceptibility.
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    Acute Cannabinoids Produce Robust Anxiety-Like and Locomotor Effects in Mice, but Long-Term Consequences Are Age- and Sex-Dependent
    (Frontiers Media, 2019-02-20) Kasten, Chelsea R.; Zhang, Yanping; Boehm, Stephen L., II; Department of Psychology, School of Science
    The rise in cannabinoid legalization and decriminalization in the US has been paired with an increase in adolescents that perceive marijuana as a "no risk" drug. However, a comprehensive review of human literature indicates that cannabinoid usage may have both beneficial and detrimental effects, with adolescent exposure being a critical window for harming cognitive development. Although the cannabinoids Δ9-tetrahydrocannabinol (THC) and cannabidiol (CBD) are often used together for recreational and medical purposes, no study has previously observed the acute and long-lasting effects of THC+CBD in a battery of behavioral assays analogous to subjective human reports. The current study observed the acute and long-term effects of THC, CBD, and THC+CBD on object recognition memory, anxiety-like behavior, and activity levels in adolescent and adult mice of both sexes. Acute THC alone and in combination with CBD resulted in robust effects on anxiety-like and locomotor behavior. A history of repeated cannabinoid treatment followed by a period without drug administration resulted in minimal effects in these behavioral assays. Most notably, the strongest effects of repeated cannabinoid treatment were seen in adult females administered THC+CBD, which significantly impaired their object recognition. No effects of repeated cannabinoid history were present on hippocampal protein expression. These studies represent a detailed examination of age- and sex-effects of acute and repeated cannabinoid administration. However, the acute and long-term effects of THC with and without CBD on additional behaviors in adolescents and adults will need to be examined for a more complete picture of these drug effects.
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    Effects of acute and repeated cannabinoid injections on immediate and delayed object memory and unconditioned anxiety – a developmental trajectory
    (2017-05) Kasten, Chelsea; Boehm II, Stephen L.; Czachowski, Cristine; Neal-Beliveau, Bethany; Powley, Terry
    Cannabinoid receptors (CBRs) are inhibitory G-protein coupled receptors (GPCRs) that bind endogenous and exogenous cannabinoids. In an unaltered state, endogenous cannabinoids regulate system function and synchrony. Administration of cannabinoids such as Δ9-tetrahydrocannabinol (THC) and cannabidiol (CBD), which are found in the cannabis plant, can lead to disruptions in well-maintained inhibitory signaling. Although marijuana usage rates have been relatively stable since 2002, the number of young adolescents and adults that report perceiving marijuana as a “no risk” drug has doubled to more than 17% in each age group (Azofeifa et al., 2016). However, no drug is fully without risks. Preclinical studies have indicated that a history of THC during adolescence, but not adulthood, results in object memory impairments following a period of no-drug administration. In tests of unconditioned anxiety, acute THC evokes anxiety-like activity at higher doses. Conversely, CBD blocks object memory impairment in models that produce inflammation and also produces anxiolytic activity. Although THC and CBD are often used together for recreational and medical purposes, no study has observed the acute and long-lasting effects of THC+CBD in a battery of tests. The current work sought to fulfill three specific aims of research to identify both age and sex differences in response to cannabinoids. In Aim 1, a dose-response to acute THC or CBD was assessed in male and female adolescent and adult mice on the elevated plus maze (EPM) and open field (OF) activity. In Aim 2, acute vehicle, 10 mg/kg THC, 20 mg/kg CBD, and THC+CBD were assessed for their effects on memory consolidation, EPM, and OF activity in male and female mice during adolescence or adulthood. Mice from Aim 2 received a total of 8 injections over a 3 week period, then were given 3 weeks of rest. In Aim 3, all mice were tested again for object memory, EPM, and OF activity under no-drug conditions to assess the effects of an adolescent or adult history of cannabinoids in male and female mice. Results of Aim 1 indicated that adult mice, regardless of sex, were more sensitive to the acute effects of THC on unconditioned anxiety and locomotor activity. A rapid tolerance to THC may develop, as mice tested on the EPM in Aim 2 following their second injection of THC did not demonstrate anxiety-like activity that was present in Aim 1. However, anxiety-like activity persisted in the open field, and acute administration of THC+CBD resulted in synergistic effects on anxiety in adult females over THC alone. Interestingly, acute THC in adolescent males rescued a deficit in object memory in the vehicle group, whereas only adult males receiving vehicle showed significant object discrimination. Females were relatively resistant to effects of acute cannabinoids on object memory, with adolescents being completely insensitive. Results of Aim 3 indicated minimal effects of a history of cannabinoids on behavior. In contrast to previous experiments, an adolescent history of THC did not impair object memory. Interestingly, females administered THC+CBD during adulthood demonstrated impaired object memory following a no-drug period. Although CBD is often considered to lack a psychoactive profile, it is hypothesized that this impairment may be due to actions of CBD on 5HT1a receptors and require a fully-developed stress and gonadal system. The current results indicate that acute cannabinoid administration results in anxiety-like behavior when administered during adulthood, and that an adult history of THC+CBD in females results in impaired cognitive behavior. As the effects of cannabinoids were primarily present in adults, this may suggest that the fully-developed brain is more susceptible to interruption by acute and repeated exogenous cannabinoid administration and that adolescents may have a higher threshold for impairment of behavior.
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    Examining Simultaneous Alcohol and ∆9-Tetrahydrocannabinol Self-Administration on Behavioral Flexibility and Dorsal Striatal CB1 Expression in cHAP Mice
    (2020-08) Millie, Lauren A.; Grahame, Nicholas; Boehm, Stephen; Logrip, Marian; Mackie, Ken
    Although marijuana and alcohol are two of the most commonly used drugs in the United States, relatively little is understood about how these drugs interact to effect drug use, cognitive behaviors, and neurophysiological changes. Specific drug use patterns such as simultaneous use may produce differential effects for consumption and other behaviors in addition to unique neurobiological changes compared to singular drug use. In order to better understand the effects of simultaneous alcohol and marijuana (SAM) use, we used the selectively bred crossed High Alcohol Preferring mice to examine consummatory, cognitive, and neurobiological changes following chronic alcohol and THC self-administration. We hypothesized that SAM mice would consume more drug than animals exposed to either substance alone. We used an operant behavioral flexibility paradigm to assess cognitive impairments believing that drug-exposed animals would show deficits relative to Control animals, with SAM mice being the most impaired of all drug conditions. Finally, we assessed CB1 receptor changes in the dorsal striatum, as this region is critical for behavioral flexibility (Bissonette & Powell, 2012; Ragozzino, 2007), CB1 receptors are the primary target of THC and these receptors are involved in numerous alcohol related behaviors (Maldonado et al., 2006; Pava & Woodward, 2012). Contrary to our hypothesis, SAM animals did not consume higher levels of drug compared to mice exposed to only THC or alcohol. Interestingly, female THC consumption was robust when THC was consumed alone but was reduced when simultaneous access to alcohol was available. Surprisingly, although we speculated that drug-exposed mice would be impaired compared to Control animals, and that SAM animals would likely be more compromised than THC and alcohol for Reversal Learning and Attentional Set-Shifting respectively, behavioral flexibility deficits were absent in our paradigm. Finally, alterations to dorsal striatal CB1 receptor expression were observed following a Short Abstinence period. Despite an absence of cognitive behavioral effects, this research contributes to furthering our understanding of co-drug use for consummatory and neurobiological changes, both of which are critically necessary given the evolving landscape surrounding simultaneous alcohol and recreational marijuana use.
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    Marijuana and Opioid Use during Pregnancy: Using Zebrafish to Gain Understanding of Congenital Anomalies Caused by Drug Exposure during Development
    (MDPI, 2020-08-08) Sarmah, Swapnalee; Sales Cadena, Marilia Ribeiro; Cadena, Pabyton Gonçalves; Marrs, James A.; Biology, School of Science
    Marijuana and opioid addictions have increased alarmingly in recent decades, especially in the United States, posing threats to society. When the drug user is a pregnant mother, there is a serious risk to the developing baby. Congenital anomalies are associated with prenatal exposure to marijuana and opioids. Here, we summarize the current data on the prevalence of marijuana and opioid use among the people of the United States, particularly pregnant mothers. We also summarize the current zebrafish studies used to model and understand the effects of these drug exposures during development and to understand the behavioral changes after exposure. Zebrafish experiments recapitulate the drug effects seen in human addicts and the birth defects seen in human babies prenatally exposed to marijuana and opioids. Zebrafish show great potential as an easy and inexpensive model for screening compounds for their ability to mitigate the drug effects, which could lead to new therapeutics.
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    Short-Term Genetic Selection for Adolescent Locomotor Sensitivity to Delta9-Tetrahydrocannabinol (THC)
    (Springer Nature, 2018-05) Kasten, Chelsea R.; Zhang, Yanping; Mackie, Ken; Boehm, Stephen L., II; Psychology, School of Science
    Cannabis use is linked to positive and negative outcomes. Identifying genetic targets of susceptibility to the negative effects of cannabinoid use is of growing importance. The current study sought to complete short-term selective breeding for adolescent sensitivity and resistance to the locomotor effects of a single 10 mg/kg THC dose in the open field. Selection for THC-locomotor sensitivity was moderately heritable, with the greatest estimates of heritability seen in females from the F2 to S3 generations. Selection for locomotor sensitivity also resulted in increased anxiety-like activity in the open field. These results are the first to indicate that adolescent THC-locomotor sensitivity can be influenced via selective breeding. Development of lines with a genetic predisposition for THC-sensitivity or resistance to locomotor effects allow for investigation of risk factors, differences in consequences of THC use, identification of correlated behavioral responses, and detection of genetic targets that may contribute to heightened cannabinoid sensitivity.
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    URINE THC METABOLITE LEVELS CORRELATE WITH STRIATAL D2/D3 RECEPTOR AVAILABILITY
    (Office of the Vice Chancellor for Research, 2012-04-13) Albrecht, Daniel S.; Skosnik, Patrick D.; Vollmer, Jennifer M.; Brumbaugh, Margaret S.; Perry, Kevin M.; Zheng, Qi-Huang; Federici, Lauren A.; Patton, Elizabeth A.; Herring, Christine M.; Yoder, Karmen K.
    Rationale: Although the incidence of cannabis abuse/dependence in Americans is rising, the neurobiology of cannabis addiction is not well understood. Previous PET and SPECT studies have demonstrated deficits in striatal D2/D3 receptor availability in several substance-dependent populations. However, this has not been studied in chronic cannabis users. Objective: The purpose of this study was to compare striatal D2/D3 receptor availability between currently-using chronic cannabis users and healthy controls. Methods: Eighteen right-handed males, 18-34 years of age, were studied. Ten subjects were chronic cannabis users; eight were demographically matched controls. Subjects underwent a [11C]raclopride (RAC) PET scan. On the scan day, urine samples were obtained from cannabis users for quantification of urine Δ-9-tetrahydrocannabinol (THC; the active compound in cannabis smoke) and THC metabolites (11-nor-Δ-9-THC-9-carboxylic acid and 11-hydroxy-THC). Striatal RAC binding potential (BPND) was used as an index of D2/D3 receptor availability; this parameter was estimated at each image voxel for every subject. SPM5 software was used to test for differences in BPND between groups and, in cannabis subjects, for associations between BPND and markers of cannabis use. Results: There were no differences in D2/D3 receptor availability between cannabis users and controls. Smokers of either cannabis and/or tobacco had 10.2% lower BPND values than nonsmokers in the bilateral putamen (“any-smokers”: 2.66 ± 0.2; nonsmokers: 2.97 ± 0.2). In cannabis users, RAC BPND values were negatively associated with both urine levels of cannabis metabolites and self-report of recent cannabis consumption. Conclusions: There is an inverse relationship between chronic cannabis use and striatal RAC BPND. This may be caused by inhibition of monoamine oxidase (MAO) by the pyrolyzation of cannabis, which could lead to increased endogenous dopamine levels (and hence, lower BPND in heavier users). Additional studies are needed to identify the neurochemical consequences of chronic cannabis use on the dopamine system.