Marijuana, immunity and infection

The influence of marijuana cannabinoids on immune function has been examined extensively over the last 25 yr. Various experimental models have been used employing drug-abusing human subjects, experimental animals exposed to marijuana smoke or injected with cannabinoids, and in vitro models employing immune cell cultures treated with various cannabinoids. For the most part, these studies suggest that cannabinoids modulate the function of T and B lymphocytes as well as NK cells and macrophages. In addition to studies examining cannabinoid effects on immune cell function, other reports have documented that these substances modulate host resistance to various infectious agents. Viruses such as herpes simplex virus and murine retrovirus have been studied as well as bacterial agents such as members of the genera Staphylococcus, Listeria, Treponema, and Legionella. These studies suggest that cannabinoids modulate host resistance, especially the secondary immune response. Finally, a third major area of host immunity and cannabinoids is that involving drug effects on the cytokine network. Employing in vivo and in vitro models, it has been determined that cannabinoids modulate the production and function of acute phase and immune cytokines as well as modulate the activity of network cells such as macrophages and T helper cells, Th1 and Th2. These results are intriguing and demonstrate that under certain conditions, cannabinoids can be immunomodulatory and enhance the disease process. However, more studies are needed to determine both the health risk of marijuana abuse and the role of the cannabinoid receptor/ligand system in immune regulation and homeostasis.     

Marijuana as a medicine

Determination of level of CA 19-9 cancer-embryonal antigen (CEA) and alpha-fetoprotein (AFP) is an objective test in the diagnosis of gastric, pancreatic and colonic cancer and may be applied for prognosis and estimation of the treatment efficacy.     

Marijuana usage and hypnotic susceptibility.

Obtained anonymous self-reported drug usage data and Harvard Group Scale of Hypnotic Susceptibility scores from 282 college students. Frequent marihuana users (more than 10 times) showed greater susceptibility to hypnosis than nonusers. There were no differences in primary suggestibility between principled nonusers and nonusers or between single-time, occasional, and frequent users. Frequent smoking of marihuana was significantly associated with S's sex, academic major, religion, family income, previous trancelike experience, and the usage of other major drugs. Frequency of drug usage data were compared with other major surveys. Findings are discussed in terms of sensation seeking and previously reported personality characteristics of marihuana users. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Marijuana. Respiratory tract effects

Daily marijuana smoking has been clearly shown to have adverse effects on pulmonary function and produce respiratory symptomatology (cough, wheeze, and sputum production) similar to that of tobacco smokers. Based on the tobacco experience, decrements in pulmonary function may be predictive of the future development of chronic obstructive pulmonary disease (COPD). However, in the absence of alpha-1-antitrypsin deficiency, the habitual marijuana-only smoker would likely have to smoke 4-5 joints per day for a span of at least 30 yr in order to develop overt manifestations of COPD. The mutagenic/carcinogenic properties of marijuana smoke are also well-established. The potential for induction of laryngeal, oropharyngeal, and possibly bronchogenic carcinoma from marijuana has been documented by several case reports and observational series. Despite this, a relative risk ratio for the development of these tumors has not yet been quantified. Based on a higher frequency of case reports for upper airway cancer compared to bronchogenic carcinoma, marijuana smoking may have a more deleterious effect on the upper respiratory tract. However, this hypothesis remains speculative at best, pending confirmation by longitudinal studies.     

Marijuana and hostility in a small-group setting

The authors used several indices to assess the relationship between marijuana and hostility as both inner affect and verbal behavior in a small-group setting. Marijuana subjects reported a small but statistically significant decrease in hostile feelings after the introduction of a frustration stimulus. They also showed significantly less verbal hostility than placebo subjects both before and after introduction of a frustration stimulus. The authors note that research findings on marijuana and hostility are not consistent and suggest a multidetermined relationship based on dose, environment, nature of the frustration stimulus, and intraindividual factors.     

Malignant hyperthermia

Malignant hyperthermia is a rare autosomal dominant trait that predisposes affected individuals to great danger when exposed to certain anaesthetic triggering agents (such as potent volatile anaesthetics and succinylcholine). A sudden hypermetabolic reaction in skeletal muscle leading to hyperthermia and massive rhabdomyolysis can occur. The ultimate treatment is dantrolene sodium a nonspecific muscle relaxant. Certain precautions should be taken before anaesthesia of patients known to be susceptible to malignant hyperthermia. These include the prohibition of the use of triggering agents, monitoring of central body temperature and expired CO2, and immediate availability of dantrolene. In addition, careful cleansing of the anaesthesia machine of vapours of halogenated agents is recommended. If these measures are taken, the chances of an MH episode are greatly reduced. When malignant hyperthermia-does occur in the operating room, prompt recognition and treatment usually prevent a potentially fatal outcome. The most reliable test to establish susceptibility to malignant hyperthermia is currently the in vitro caffeine-halothane contracture test. It is hoped that in the future a genetic test will be available.     

Marijuana use and treatment outcome in cocaine-dependent patients.

Marijuana use was assessed in 186 people seeking treatment for cocaine dependence. Comparisons were made between clients who did and did not report using marijuana and between marijuana users who did and did not meet diagnostic criteria for marijuana dependence. The relationship between marijuana use and treatment outcome was also explored. A high rate of current marijuana use (59%) was observed at intake, and the majority of the marijuana users (74%) used marijuana at some point during treatment. Marijuana use at intake was associated with increased psychosocial impairment and substance-use severity. However, no significant adverse relations were observed between marijuana use at intake or during treatment and treatment outcome. Such functional independence may have important implications for addressing marijuana use during treatment for cocaine dependence. These findings should be interpreted with caution pending replication in prospective studies and with other treatment approaches. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Marijuana and vision--after ten years' use in Costa Rica

Several tests of visual function were applied to an abstaining user (10 years or more) group and a nonuser group carefully preselected to be free of clinical signs of eye disease. The groups were matched on several criteria. The results show that all findings from both groups are within established limits of normalcy. Small differences and trends were found between the groups. These would have been undetected without large samples. Relative to the nonuser group, tests showed these user trends: increased basal lacrimation, increased intraocular pressure, increased photosensitivity, decreased dark adaptation, decreased color-match limits, and decreased Snellen acuity. These differences were associated with statistical probabilities, p=0.07 to p=0.001. There were no significant differences or clear trends between the user and nonuser groups in incidence of pathological fundus signs, conjunctival hyperemia, pterygia, or color-match midpoints.     

Malignant hyperthermia

A specific inherited muscle membrane disorder predisposes to a variety of clinical problems. The most common is malignant hyperthermia (MH), a dangerous hypermetabolic state after anaesthesia with suxamethonium and/or volatile halogenated anaesthetic agents. MH may also be triggered in susceptible individuals by severe exercise in hot conditions, infections, neuroleptic drugs, and overheating in infants. Inbred pigs have provided a helpful model, and experiments on these animals and in MH-susceptible patients have shown that the essential biochemical abnormality is an increase in calcium ions in the muscle cells. This knowledge has led to a specific muscle test to identify susceptibility to MH and to a specific treatment, dantrolene; and as a result the case-fatality rate in MH has fallen from 70% in the 1970s to 5% today. In pigs susceptibility to MH is caused by a single mutation in the ryanodine receptor (RYR) in skeletal muscle. In man the genetics is more complex and three clinical myopathies that predispose to MH have been defined. By far the most common is inherited as a mendelian dominant characteristic and at present mutations in the human RYR account for no more than 20% of susceptible families.     

Marijuana and cocaine impair alveolar macrophage function and cytokine production

Use of marijuana and cocaine is on the rise in the United States. Although pulmonary toxicity from these drugs has occasionally been reported, little is known about their effects on the lung microenvironment. We evaluated the function of alveolar macrophages (AMs) recovered from the lungs of nonsmokers and habitual smokers of either tobacco, marijuana, or crack cocaine. AMs recovered from marijuana smokers were deficient in their ability to phagocytose Staphylococcus aureus (p < 0.01). AMs from marijuana smokers and from cocaine users were also severely limited in their ability to kill both bacteria and tumor cells (p < 0.01). Studies using NG-monomethyl-L-arginine monoacetate, an inhibitor of nitric oxide synthase, suggest that AMs from nonsmokers and tobacco smokers were able to use nitric oxide as an antibacterial effector molecule, while AMs from smokers of marijuana and cocaine were not. Finally, AMs from marijuana smokers, but not from smokers of tobacco or cocaine, produced less than normal amounts of tumor necrosis factor-alpha, granulocyte-macrophage colony-stimulating factor, and interleukin-6 when stimulated in culture with lipopolysaccharide. In contrast, the production of transforming growth factor-beta, an immunosuppressive cytokine, was similar in all groups. These findings indicate that habitual exposure of the lung to either marijuana or cocaine impairs the function and/or cytokine production of AMs. The ultimate outcome of these effects may be an enhanced susceptibility to infectious disease, cancer, and AIDS.     

Selective hyperthermia and reaction time

Two reaction time studies are reported in which subjects responded under conditions of selective hyperthermia. Wearing a helmet prototype, the cortical surface of the subject was thermally stressed to a level 1.11 degrees C over baseline as measured by a thermocouple placed against the tympanic membrane. In a simple choice RT task, both reaction time and response variability were decreased compared to performance in either a control or placebo condition. Latency in Neisser's visual scanning task was also shortened under conditions of this thermal stress localized in the cortical region. In both cases, there was no observed decrement in accuracy or level of performance. Enhanced human performance resulting from the maintenance of cortical temperature above the normal diurnal range is implied.     

Suxamethonium-induced porcine malignant hyperthermia

Metabolic, haemodynamic and neuroendocrine responses to suxamethonium (SCh) were measured in five normal swine and five swine susceptible to malignant hyperthermia (MH), to compare the responses with those previously reported for halothane. Following SCh, the onset of MH was sooner and more abrupt than following halothane. The maximal changes in aerobic metabolism and body temperature sere similar, while the changes in lactate, potassium, hydrogen ion and catecholamine concentrations were smaller than those observed following halothane. These results are discussed in terms of the action of chemical depolarizing drugs such as suxamethonium and acetylcholine. The propagated muscle action potentials produce an increase in the free intracellular calcium concentration which may be self-regenerative, but which may become uncontrollable because of the peculiarities of MH that effect the calcium pump or storage areas.     

Marijuana use and panic psychopathology among a representative sample of adults.

This study examined the relations between marijuana use and panic attacks and panic disorder using a large representative survey of adults (N = 5,672; 53% women; Mage = 45.05 years, SD = 17.9) conducted in the United States (Kessler et al., 2004). After adjusting for sociodemographic variables (age, marital status, income, education, race, and sex) and the presence of a lifetime substance use disorder, lifetime marijuana use was significantly associated with increased odds of a lifetime panic attack history. Lifetime marijuana use also was significantly associated with an increased risk of current (past-year) panic attacks; however, this relation was not significant when controlling for nicotine dependence. Lifetime marijuana use was significantly associated with increased odds of a lifetime diagnosis of panic disorder as well as a current (past-year) diagnosis of panic disorder. Current (past-year) marijuana use was significantly associated with both lifetime and current panic attacks, but not current or lifetime panic disorder. Results are discussed in relation to the novel information they offer in regard to understanding the putative marijuana use–panic psychopathology association(s). (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Canine hyperthermia with cerebral protection

The influence of ATP and AMP injected into the lateral cerebral ventricle in doses of 50, 100 and 200 mug on behavior in rats was studied. ATP in the doses administered had no effect on behavior of rats. AMP in these doses enhanced motor activity of the rats. Chemical sympathectomy by intracerebral injection of 6-hydroxy-dopamine did not affect the action of either of the compounds on behavior of rats. AMP potentiated the action of intracerbrally administered noradrenaline on behavior of the animals.     

Pheochromocytoma multi-organ crisis: nonseptic hyperthermia and shock

Pheochromocytoma usually presents with nonspecific symptoms such as headache, palpitation, chest pain and hypertension. We present a 48-year-old woman hospitalized due to a pheochromocytoma multi-organ crisis (PMC). It consists of a tetrad of symptoms: multi-organ failure, hyperthermia, encephalopathy and unstable blood pressure. Distinguishing PMC from septic shock may be difficult, and requires needs a high clinical index of suspicion.     

Coping and self-efficacy in marijuana treatment: Results from the Marijuana Treatment Project.

This study examined whether a coping-skills-based treatment for marijuana dependence operated by encouraging the use of coping skills or via other mechanisms. Participants were 450 men and women treated in the multisite Marijuana Treatment Project who were randomly assigned to motivational enhancement therapy plus cognitive-behavioral (MET-CB) treatment, motivational enhancement therapy (MET), or a delayed treatment control group. Marijuana use and coping skills were measured at baseline and at follow-ups through 15 months. Results showed that marijuana outcomes were predicted by treatment type and by coping skills use, but that the coping-skills-oriented MET-CB treatment did not result in greater use of coping skills than did the MET treatment. The results suggest that mechanisms of coping skills treatment may need to be reconceptualized. (PsycINFO Database Record (c) 2010 APA, all rights reserved)