Marijuana: effects on pulse rate, subjective estimates of intoxication and multiple measures of memory

Twelve experienced marijuana users received marijuana cigarettes containing 10 mg Δ⁹-THC or placebo in two experimental sessions each separated by a one week interval. The effects of both treatments on pulse rate, subjective estimates of intoxication, multiple measures of memory including free, serial and delayed recall, final free recall, and recognition memory were assessed. Pulse rate and subjective ratings were elevated significantly following intoxication with active marijuana in comparison to placebo. Each of the three types of recall were significantly reduced following intoxication with marijuana but no differential effects of drug on recall condition were noted. Intrusion errors were elevated on the final free recall test following intoxication but recognition memory was unaffected.     

Marijuana exposure in vivo and human lymphocyte chromosomes.

Sequential chromosome examinations of peripheral lymphocte cultures were carried out on 21 adult male volunteers who smoked natural blend marijuana cigarettes containing about 1%, 2%, or no delta9-THC. For a limited number of subjects, blood samples from a single venipuncture were cultured independently in two cytogenetic laboratories, and later the slides were exchaged for re-analysis. There were significant differences between laboratories in the absolute break frequencies recorded. These inter-laboratory differences were demonstrated for both techniques of cell culture and metaphase analysis. Neither laboratory found a statistically significant increase in break frequencies asssociated with marijuana smoking. The present study, therefore, failed to detect a measurable effect of marijuana smoking on chromosomal aberrations in subjects experienced in the use of the drug.     

Inhaled marijuana smoke disrupts mitochondrial energetics in pulmonary epithelial cells in vivo

Habitual marijuana smoking is associated with inflammation and atypia of airway epithelium accompanied by symptoms of chronic bronchitis. We hypothesized that Delta(9)-tetrahydrocannabinol (THC), the primary psychoactive component of marijuana, might contribute to these findings by impairing cellular energetics and mitochondrial function. To test this hypothesis, we examined particulate smoke extracts from marijuana cigarettes, tobacco cigarettes, and placebo marijuana (0% THC) cigarettes for their effects on the mitochondrial function of A549 cells in vitro. Only extracts prepared from marijuana cigarettes altered mitochondrial staining by the potentiometric probe JC-1. With the use of a cross-flow, nose-only inhalation system, rats were then exposed for 20 min to whole marijuana smoke and examined for its effects on airway epithelial cells. Inhalation of marijuana smoke produced lung tissue concentrations of THC that were 8-10 times higher than those measured in blood (75 +/- 38 ng/g wet wt tissue vs. 9.2 +/- 2.0 ng/ml), suggesting high local exposure. Intratracheal infusion of JC-1 immediately following marijuana smoke exposure revealed a diffuse decrease in lung cell JC-1 red fluorescence compared with tissue from unexposed or placebo smoke-exposed rats. Exposure to marijuana smoke in vivo also decreased JC-1 red fluorescence (54% decrease, P < 0.01) and ATP levels (75% decrease, P < 0.01) in single-cell preparations of tracheal epithelial cells. These results suggest that inhalation of marijuana smoke has deleterious effects on airway epithelial cell energetics that may contribute to the adverse pulmonary consequences of marijuana smoking.     

Neuropsychological effects of marijuana

This study assigned 81 non-naïve subjects, divided into low- and high-dose groups, to four experimental conditions (marijuana/marijuana, marijuana/placebo, placebo/marijuana and placebo/placebo) for two sessions separated by about one week. The low dose was 4.8 mg. Δ⁹-THC followed by 2.4 mg. one hour later. The high dose was 9.1 mg. followed by 4.5 mg. one hour later. A battery of neuropsychological tests was administered.The low dose produced generalized impairment of all mental processes (concept formation, memory, tactile form discrimination and motor function) and the effect was generalized to all modalities. The high dose resulted in more extensive impairment, again generalized.The drug effects noted were explained in terms of generalized impairment of central integrative processes. The effects of marijuana on learning as well as memory were explained in terms of impaired output (recall), but the impairment was transient.     

The neurophysiological basis of the marijuana experience

Experiments were done with 75 healthy young adults to explore the neurophysiological basis of the acute marijuana intoxication state. Tests included recording the scalp EEG, visual and auditory cerebral evoked-potentials, the CNV, cerebral slow potentials related to certainty of response correctness in auditory discrimination tasks, heart rate, respiration and the galvanic skin response. All variables were recorded over 45 minutes before and 45 minutes after smoking a marijuana cigarette containing either 4.8, 9.1 or less than 0.01 mg. Δ⁹-THC.High doses of marijuana induced a significant decrease in the peak power of the alpha rhythm and an increase in auditory evoked-response latency. The CNV increased in ampiitude after smoking marijuana in low doses and sequential CNVs showed changes consistent with sustained attention but decreased certainty about performance following either low or high dose. Marijuana interfered significantly with performance of the discrimination task itself.     

Low platelet monoamine oxidase activity and chronic marijuana use

Mean platelet monoamine oxidase (MAO) activity in 26 consecutively-studied male marijuana smokers was significantly lower than in a comparable group of non-marijuana smoking males. In addition, the level of current marijuana use reported by the subjects was significantly and inversely correlated with MAO activity. No acute reduction in MAO activity was found in response to smoking a marijuana cigarette containing 15 mg of delta-9-THC. Significant $\text{in vitro}$ inhibition of MAO activity by THC was detected only at THC concentrations above 10^?5M, approximately 100 times the peak plasma concentrations seen $\text{in vivo}$ following smoking.     

Selective REM Sleep Deprivation Improves Expectation-Related Placebo Analgesia

The placebo effect is a neurobiological and psychophysiological process known to influence perceived pain relief. Optimization of placebo analgesia may contribute to the clinical efficacy and effectiveness of medication for acute and chronic pain management. We know that the placebo effect operates through two main mechanisms, expectations and learning, which is also influenced by sleep. Moreover, a recent study suggested that rapid eye movement (REM) sleep is associated with modulation of expectation-mediated placebo analgesia. We examined placebo analgesia following pharmacological REM sleep deprivation and we tested the hypothesis that relief expectations and placebo analgesia would be improved by experimental REM sleep deprivation in healthy volunteers. Following an adaptive night in a sleep laboratory, 26 healthy volunteers underwent classical experimental placebo analgesic conditioning in the evening combined with pharmacological REM sleep deprivation (clonidine: 13 volunteers or inert control pill: 13 volunteers). Medication was administered in a double-blind manner at bedtime, and placebo analgesia was tested in the morning. Results revealed that 1) placebo analgesia improved with REM sleep deprivation; 2) pain relief expectations did not differ between REM sleep deprivation and control groups; and 3) REM sleep moderated the relationship between pain relief expectations and placebo analgesia. These results support the putative role of REM sleep in modulating placebo analgesia. The mechanisms involved in these improvements in placebo analgesia and pain relief following selective REM sleep deprivation should be further investigated.     

The effects of 9-ene-tetrahydrocannabinol on hormone release and immune function

We investigated effects of 9-ene-tetrahydrocannabinol (THC) on endocrine and immunological function. Seventeen male volunteers entered into a double blind, randomized study to receive oral THC (10 mg t.i.d. for 3 days and on the morning of the fourth day) or placebo, after at least 2 weeks of abstinence. Plasma prolactin, ACTH, cortisol, luteinizing hormone and testosterone were not altered during or after THC, compared with baseline concentrations. Tests of lymphocyte function showed no differences compared to baseline between THC and placebo groups. As the relatively low dosing regimen of THC (10 mg t.i.d.) resulted in no alterations, another group of 6 men were administered higher doses of THC by inhalation (18 mg/marijuana cigarette) following the same dosing regimen. No endocrine or immunological alterations were observed. When the subjects were grouped according to their history of THC use prior to admission, heavy THC users had lower prolactin concentrations than light users. No differences were observed in concentrations of other hormones or in tests of immune function.     

Cannabis reinforcement and dependence: role of the cannabinoid CB1 receptor.

Awareness of cannabis dependence as a clinically relevant issue has grown in recent years. Clinical and laboratory studies demonstrate that chronic marijuana smokers can experience withdrawal symptoms upon cessation of marijuana smoking and have difficulty abstaining from marijuana use. This paper will review data implicating the cannabinoid CB1 receptor in regulating the behavioral effects of Delta(9)-tetrahydrocannobinol (THC), the primary psychoactive component of cannabis, across a range of species. The behavioral effects that will be discussed include those that directly contribute to the maintenance of chronic marijuana smoking, such as reward, subjective effects, and the positive and negative reinforcing effects of marijuana, THC and synthetic cannabinoids. The role of the CB1 receptor in the development of marijuana dependence and expression of withdrawal will also be discussed. Lastly, treatment options that may alleviate withdrawal symptoms and promote marijuana abstinence will be considered.     

Correlates of Marijuana Drugged Driving and Openness to Driving While High: Evidence from Colorado and Washington

Aims

A potential unintended consequence of legalizing recreational marijuana is increased marijuana-related driving impairment. Some states where recreational marijuana is legal have begun implementing interventions to mitigate driving under the influence (DUI) of marijuana, including media campaigns to increase knowledge about DUI laws. However, little is known about the associations between knowledge of DUI laws and marijuana DUI behavior. In this study, we provide new data from a survey of marijuana users in Colorado and Washington to examine associations between marijuana drugged driving and two potential behavioral precursors of marijuana DUI. We also explore other factors that may influence marijuana DUI.

Methods

Data are from an online survey of marijuana users in Colorado and Washington. Respondents who reported any marijuana use in the past 30 days (n = 865) served as the analytic sample. We examined prevalence of two behavioral outcomes: (1) any driving of a motor vehicle while high in the past year and (2) driving a motor vehicle within 1 hour of using marijuana 5 or more times in the past month. Additional outcomes measuring willingness to drive while high were also assessed. Logistic regressions were used to estimate each outcome as a function of two multi-item scales measuring knowledge of the legal consequences of driving high and perceptions that driving while high is not safe. Additional covariates for potential confounders were included in each model.

Results

Prevalence of past-year driving while under the influence of marijuana was 43.6% among respondents. The prevalence of driving within 1 hour of using marijuana at least 5 times in the past month was 23.9%. Increased perception that driving high is unsafe was associated with lower odds of past-year marijuana DUI (OR = 0.31, P < 0.01) and lower past-month odds of driving 5 or more times within 1 hour of using marijuana (OR = 0.26, P < 0.01). Increased knowledge of marijuana DUI laws was also associated with lower odds of each of these outcomes (OR = 0.63, P < 0.01, OR = 0.69, P = 0.02, respectively). Post-estimation Wald tests confirmed the negative associations with marijuana DUI were greater in magnitude for safety perceptions than knowledge of DUI laws. Increased perceptions that driving while high is unsafe was associated with significantly lower willingness to drive after using marijuana while increased knowledge of marijuana DUI laws was not associated with these outcomes.

Conclusions

Despite recent interventions targeting public awareness of the legal consequences of marijuana DUI, our results suggest that knowledge of these laws is a weaker predictor of DUI behavior than perceptions that driving high is unsafe. In addition, safety perceptions predict decreased openness to driving high while knowledge of DUI laws was not associated with openness. These findings suggest that interventions for reducing the incidence of marijuana DUI are likely to be more successful by targeting safety perceptions related to marijuana DUI rather than knowledge of DUI laws. We caution that because these data are limited to an online convenience sample, results may not be generalizable beyond our sample.     

Allergic Skin Test Reactivity to Marijuana in the Southwest

In a general allergy consultation practice in Arizona and western New Mexico, 129 patients were tested for immediate hypersensitivity skin test reactivity to marijuana pollen and tobacco leaf, as well as to a battery of other antigens. In all, 90 patients were diagnosed as allergic (atopic) and, of these, 63 (70 percent) were found to be skin test reactive to marijuana pollen and 18 (20 percent) to tobacco leaf. The incidence of skin test reactivity to marijuana was not significantly different for persons living at low, middle or high elevations throughout the Southwest. Marijuana sensitivity occurred in patients who were, in general, also sensitive to a variety of other airborne plant pollens. There was no close correlation, however, between sensitivity to marijuana pollen and sensitivity to pollens from elm, mulberry, hop and stinging nettle, which are botanically related to marijuana. The data suggest that marijuana pollen may be a relatively common airborne pollen pollutant in the Southwest, allergic persons being sensitized through inhalation. If this is confirmed by further studies, then clinical investigation of marijuana hyposensitization (immunotherapy) may be warranted. This is in contrast to tobacco allergy for which simple avoidance is recommended.     

Focus: Sex and Gender Health: Marijuana,the Endocannabinoid System and the Female Reproductive System

Marijuana use among women is highly prevalent, but the societal conversation on marijuana rarely focuses on how marijuana affects female reproduction and endocrinology. This article reviews the current scientific literature regarding marijuana use and hypothalamic-pituitary-ovarian (HPO) axis regulation, ovarian hormone production, the menstrual cycle, and fertility. Evidence suggests that marijuana can reduce female fertility by disrupting hypothalamic release of gonadotropin releasing hormone (GnRH), leading to reduced estrogen and progesterone production and anovulatory menstrual cycles. Tolerance to these effects has been shown in rhesus monkeys, but the effects of chronic marijuana use on human female reproduction are largely unknown. Marijuana-induced analgesia, drug reinforcement properties, tolerance, and dependence are influenced by ovarian hormones, with estrogen generally increasing and progesterone decreasing sensitivity to marijuana. Carefully controlled regulation of the Endocannabinoid System (ECS) is required for successful reproduction, and the exogenous cannabinoids in marijuana may disrupt the delicate balance of the ECS in the female reproductive system.     

Reefer Madness: Legal & Moral Issues Surrounding the Medical Prescription of Marijuana

California, Arizona, and several other states have recently legalized medical marijuana. My goal in this paper is to demonstrate that even if one grants the opponents of legalization many of their contentious assumptions, the federal government is still obligated to take several specific steps toward the legalization of medical marijuana. I defend this claim against a variety of objections, including the claims: that marijuana is unsafe, that marijuana cannot be adequately tested or produced as a drug, that the availability of synthetic THC makes marijuana superfluous, and especially that legalizing medical marijuana will increase recreational use by 'sending the wrong message '. I then go on to argue that given the intransigent position of the federal government on this issue, state governments are justified in unilaterally legalizing medical marijuana as an act of civil disobedience.
A large portion of this paper consists of an extensive response to the objection that legalizing medical marijuana will 'send the wrong message '– which I take to be the primary impediment to legalization. This objection basically claims that the consequences of withholding legalization (especially preventing increased recreational use) are superior to those of legalizing medical marijuana. I argue that legalization is justified even if one were to grant both that the harms of legalization outweighed its benefits and that utilitarianism is true. This requires a subtle and somewhat extended discussion of utilitarian moral and political theory.     

The effects of chronic marijuana use on circadian entrainment

Animal literature suggests a connection between marijuana use and altered circadian rhythms. However, the effect has not yet been demonstrated in humans. The present study examined the effect of chronic marijuana use on human circadian function. Participants consisted of current users who reported smoking marijuana daily for at least a year and non-marijuana user controls. Participants took a neurocognitive assessment, wore actigraphs and maintained sleep diaries for three weeks. While no significant cognitive changes were found between groups, data revealed that chronic marijuana use may act as an additional zeitgeber and lead to increased entrainment in human users.     

Prospects for cannabinoids as anti-inflammatory agents

The marijuana plant (Cannabis sativa) and preparations derived from it have been used for medicinal purposes for thousands of years. It is likely that the therapeutic benefits of smoked marijuana are due to some combination of its more than 60 cannabinoids and 200-250 non-cannabinoid constituents. Several marijuana constituents, the carboxylic acid metabolites of tetrahydrocannabinol, and synthetic analogs are free of cannabimimetic central nervous system activity, do not produce behavioral changes in humans, and are effective antiinflammatory and analgesic agents. One cannabinoid acid in particular, ajulemic acid, has been studied extensively in in vitro systems and animal models of inflammation and immune responses. This commentary reviews a portion of the work done by investigators interested in separating the medicinal properties of marijuana from its psychoactive effects. Understanding the mechanisms of the therapeutic effects of nonpsychoactive cannabinoids should lead to development of safe effective treatment for several diseases, and may render moot the debate about "medical marijuana".     

Effects of marijuana on testosterone in male subjects

Clinical studies have given contradictory reports on the effect of smoking marijuana on the plasma levels of testosterone in males. A reanalysis of existing data established that testosterone levels are depressed both after smoking one marijuana cigarette and after intravenous infusion of delta-9-tetrahydrocannabinol, a pharmacologically active component of marijuana. Simulation of the marijuana interaction, under the assumption that delta-9-tetrahydrocannabinol inhibits testosterone production or secretion, suggests a minimum of 24 hours are required for testosterone to return to pre-smoking levels. A series of clinical studies are specified to clarify the nature of the interaction.     

Pulmonary complications of smoked substance abuse.

After tobacco, marijuana is the most widely smoked substance in our society. Studies conducted within the past 15 years in animals, isolated tissues, and humans indicate that marijuana smoke can injure the lungs. Habitual smoking of marijuana has been shown to be associated with chronic respiratory tract symptoms, an increased frequency of acute bronchitic episodes, extensive tracheobronchial epithelial disease, and abnormalities in the structure and function of alveolar macrophages, key cells in the lungs'' immune defense system. In addition, the available evidence strongly suggests that regularly smoking marijuana may predispose to the development of cancer of the respiratory tract. "Crack" smoking has become increasingly prevalent in our society, especially among habitual smokers of marijuana. New evidence is emerging implicating smoked cocaine as a cause of acute respiratory tract symptoms, lung dysfunction, and, in some cases, serious, life-threatening acute lung injury. A strong physician message to users of marijuana, cocaine, or both concerning the harmful effects of these smoked substances on the lungs and other organs may persuade some of them, especially those with drug-related respiratory complications, to quit smoking.     

Interaction of 5HTTLPR and Marijuana Use on Property Offending

This study uses data from the National Longitudinal Study of Adolescent Health to examine whether a polymorphism in the serotonin transporter gene (5HTTLPR) moderates the effects of marijuana use on property offending. The results reveal that 5HTTLPR interacts with marijuana use to predict significantly higher levels of property offending for African American females. The interaction coefficient is not statistically significant for Caucasian males, African American males, or Caucasian females. These findings suggest that marijuana use is associated only with higher levels of property offending among African American females who carry one or more copies of the 5HTTLPR short allele.     

Marijuana: A Realistic Approach

Much of the current confusion concerning marijuana has been caused by a lack of definition of terms. Variations in drug effect that are related to the type and potency of cannabis preparation and route of administration need clarification.When domestic strength marijuana is smoked recreationally, the subjective effects include relaxation, mild euphoria and increased sensory awareness. The objective effects include tachycardia, reddening of the conjunctivae and a distorted sense of time. Undesirable effects such as panic reactions, amotivational behavior, and acute toxic psychosis occur infrequently and are reversible with proper therapy. Other effects which have been attributed to marijuana are unsubstantiated.The recent upsurge in use of marijuana involves persons of a different type than those who used it heretofore and has greatly increased the number of people familiar with the drug. The disparity between what many people know empirically and the information disseminated through official media has lessened the credibility of physicians with many of our younger citizens. When young people recognize misinformation about marijuana, they are no longer listening when the facts are presented about more dangerous drugs, and the abuse of these drugs must be our main concern. To be considered is the potential hazard to adolescent users who may concomitantly be exposed to a subculture of experimentation with stronger drugs at a time when the opinion of a peer group is a strong factor in their behavior.     

Impacts of Surface Water Diversions for Marijuana Cultivation on Aquatic Habitat in Four Northwestern California Watersheds

Marijuana (Cannabis sativa L.) cultivation has proliferated in northwestern California since at least the mid-1990s. The environmental impacts associated with marijuana cultivation appear substantial, yet have been difficult to quantify, in part because cultivation is clandestine and often occurs on private property. To evaluate the impacts of water diversions at a watershed scale, we interpreted high-resolution aerial imagery to estimate the number of marijuana plants being cultivated in four watersheds in northwestern California, USA. Low-altitude aircraft flights and search warrants executed with law enforcement at cultivation sites in the region helped to validate assumptions used in aerial imagery interpretation. We estimated the water demand of marijuana irrigation and the potential effects water diversions could have on stream flow in the study watersheds. Our results indicate that water demand for marijuana cultivation has the potential to divert substantial portions of streamflow in the study watersheds, with an estimated flow reduction of up to 23% of the annual seven-day low flow in the least impacted of the study watersheds. Estimates from the other study watersheds indicate that water demand for marijuana cultivation exceeds streamflow during the low-flow period. In the most impacted study watersheds, diminished streamflow is likely to have lethal or sub-lethal effects on state-and federally-listed salmon and steelhead trout and to cause further decline of sensitive amphibian species.