An approach to the medical marijuana controversy.

The use of smoked marijuana as a therapeutic agent is presently a matter of considerable debate in the United States. Many people suffering from a variety of disorders maintain that it is necessary for their adequate treatment. Yet, the evidence to support claims is insufficient for FDA approval. An interim solution is proposed which would allow patients referred by their physicians to participate in a 6-month program of legal marijuana availability, similar to the 'compassionate IND' program of a number of years ago. A technique similar to that used for post-marketing surveillance is proposed for obtaining quantitative data for a limited number of potential indications. These are: (1) nausea and vomiting associated with cancer chemotherapy or other causes, (2) weight loss associated with debilitating illnesses, (3) spasticity secondary to neurological diseases, and (4) chronic pain syndromes.

Calcium channel blockers in psychiatric disorders: a review of the literature.

OBJECTIVES: To review the published literature of the past 15 years regarding use of calcium channel blockers (CCBs) in psychiatric practice. These drugs, especially verapamil, have been recommended as possible treatments for mania and other disorders. METHODS: The Cumulative Medical Index and other databases were searched and back-tracked to locate relevant articles. Sixty-one such articles were uncovered: 37 anecdotal reports, 7 partially controlled reports, and 17 controlled trials. RESULTS: Most studies involved treatment of mania using verapamil. Although anecdotal reports were generally favourable, results from partially controlled reports or controlled clinical trials were mixed. Generally, verapamil was less effective than was lithium or placebo. Treatment of depression with CCBs was not very successful, regardless of the type of trial; the best trial was negative. The same was true for the treatment of schizophrenia, although the cases studied were extremely chronic and treatment-resistant. Evidence for efficacy in other illnesses, such as Alzheimer's disease or tardive dyskinesia was scanty but suggested that further trials might be in order. CONCLUSIONS: CCBs do not at present have an established place in psychiatric treatment. Nonetheless, clinicians faced with a manic patient not responsive to other antimanic drugs, either alone or in combination, might consider adding verapamil as an adjunct. A study bearing on this specific issue is needed to determine whether or not such off-label use would really be justified.

A survey of hospital practices related to pelvic and rectal examinations of psychiatric inpatients.

Fifty-three inpatient units in Texas and Massachusetts--15 free-standing psychiatric hospitals and 38 units of general hospitals--responded to a survey to determine current practice in conducting pelvic and rectal examinations of psychiatric patients. Pelvic examinations were never done at 15 of the facilities (28 percent), and rectal examinations were never done at 12 (23 percent). The other facilities did these examinations selectively based on patients' clinical history. Because selective use of these examinations is consistent with recommendations of the American Psychiatric Association and because hospitals that conduct examination selectively have received approval by the Joint Commission on Accreditation of Healthcare Organizations, it appears that selective rather than routine pelvic and rectal examinations are now considered reasonable practice.

Structural brain scanning in psychiatric patients: a further look.

BACKGROUND: Indications for computed tomographic (CT) and magnetic resonance (MR) scans of the brain in psychiatric patients are not clearly defined. This survey attempted to refine indications suggested by an earlier survey. METHOD: All brain scans ordered in a psychiatric teaching hospital were surveyed over a period of approximately 23 months. A revised order sheet provided information about the assumed need for scanning as well as indicated those factors from the previous survey most likely to reveal pertinent information. Scan results were later correlated with this information. RESULTS: Of 68 scans reviewed, 40 were normal, 16 equivocal, and 12 were abnormal. Cognitive decline and/or confusion were indications for 30 scans; 7 were abnormal, all meriting a clinical diagnosis of Alzheimer dementia. Only 1 of 12 scans to investigate a history of head injury was abnormal. Only 2 of 11 scans based on a history of seizures were abnormal; all had other possible indications. In one patient a prior stroke was confirmed, and in another, active multiple sclerosis. Ten of the group of 12 abnormal scans were found in patients over the age of 40 years, emphasizing the influence of age. CONCLUSION: Revised indications based on this second survey were as follow: (1) The importance of new or unexplained focal neurologic signs was confirmed; (2) Scans are useful for bolstering a clinical diagnosis of Alzheimer disease; (3) A first psychotic break or personality change after the age of 50 years will require investigation; (4) Cognitive decline in a patient with a prior history of functional psychosis is most likely part of the psychosis rather than a confounding organic disorder; (5) Isolated seizures of long duration or abnormal EEG without other clinical findings are seldom associated with abnormal scans.

Brain glucose metabolism in chronic marijuana users at baseline and during marijuana intoxication.

Despite the widespread abuse of marijuana, knowledge about its effects in the human brain is limited. Brain glucose metabolism with and without delta 9 tetrahydrocannabinol (THC) (main psychoactive component of marijuana) was evaluated in eight normal subjects and eight chronic marijuana abusers with positron emission tomography. At baseline, marijuana abusers showed lower relative cerebellar metabolism than normal subjects. THC increased relative cerebellar metabolism in all subjects, but only abusers showed increases in orbitofrontal cortex, prefrontal cortex, and basal ganglia. Cerebellar metabolism during THC intoxication was significantly correlated with the subjective sense of intoxication. The decreased cerebellar metabolism in marijuana abusers at baseline could account for the motor deficits previously reported in these subjects. The activation of orbitofrontal cortex and basal ganglia by THC in the abusers but not in the normal subjects could underlie one of the mechanisms leading to the drive and the compulsion to self-administer the drug observed in addicted individuals.

Drug treatment of Alzheimer's disease. Effects on caregiver burden and patient quality of life.

Alzheimer's disease is a devastating illness that will become more common as the population ages. Although clinical diagnosis of the illness is not certain without histological examination of the brain, and misdiagnosis may occur, broad working criteria to help diagnose the likely presence of Alzheimer's disease are available. Thoughtful clinical evaluation improves diagnostic accuracy, and appropriately diagnosed patients are critical for involvement in research into new antidementia agents. Essential to the discovery of new drugs is careful measurement of illness response. A variety of scales--some aimed at patients, others at their caregivers, and yet others for clinicians--assess Alzheimer's disease severity, progression, symptom response, and quality of life. Of note, patient response is not the only measurement of treatment benefit today. Growing interest is also being placed on tracking the possible amelioration of caregiver 'burden'. This burden refers to the psychological, physical, and material costs of providing care for an Alzheimer's patient over long periods of time. A number of scales and questionnaires have been developed and are occasionally used. Many drugs have been tried in Alzheimer's disease, but very few have produced any benefit, and this is often modest. Ergoloid mesylates, initially thought to be effective, are now considered of little value. The cholinomimetic drugs, especially the acetylcholinesterase inhibitor tacrine, have provided a very modest benefit, slowing the progression of the illness for a number of months. No cognitive improvement has been noted with the various nootropic agents such as piracetam. Early studies with levacecarnine (acetyl-L-carnitine), a substance that facilitates the use of fatty acids, memantidine, the dimethyl derivative of amantidine, and the calcium channel blocker nimodipine, have shown some promise, but require larger, more rigorous studies. As mentioned above, documenting effects in individual patients is crucial; examining for potential benefit to caregivers is a growing part of research design. Current treatment efforts will become more sophisticated as a deeper understanding of the neurobiology of Alzheimer's disease develops. For the immediate future, the goal is not cure but slowing of the disease process. Achieving this limited goal would have a substantial impact on the financial and human costs of the illness.

Brain glucose metabolism in violent psychiatric patients: a preliminary study.

Positron emission tomography with 18F-deoxyglucose was used to evaluate regional brain glucose metabolism in eight normal subjects and eight psychiatric patients with a history of repetitive violent behavior. Seven of the patients showed widespread areas of low brain metabolism. Although the location of the abnormal regions varied among patients, they showed significantly lower relative metabolic values in medial temporal and prefrontal cortices than did normal comparison subjects. These regions have been implicated as substrates for aggression and impulsivity, and their dysfunction may have contributed to the patients' violent behavior.

Electrocardiographic screening in psychiatric patients.

BACKGROUND: Present recommendations vary regarding the use of screening ECGs in psychiatric patients; therefore, this study was undertaken to determine the utility of routine screening electrocardiograms (ECGs) in hospitalized psychiatric patients. METHOD: Twelve-lead ECGs were obtained on 1006 consecutive admissions to an academic freestanding 250-bed public psychiatric hospital over a period of 2 years. RESULTS: Tracings were read as normal in 765 of 1006 cases. Tracings of 148 patients were considered to be equivocal, mainly due to nonspecific T wave abnormalities seen in 118 patients. In 29 patients, no ostensible cause for the T wave abnormalities was found. Among the remaining 80 instances, abnormalities were attributed to drug abuse. Especially prevalent was recent cocaine abuse, often with concurrent alcohol abuse (N = 30); recent alcohol abuse alone (N = 10); or concurrent psychotherapeutic drugs (lithium, N = 19; thioridazine, N = 9; and miscellaneous drugs, N = 12). Subclinical hypothyroidism was found in 5 and borderline hypokalemia in 4 patients. Ninety-three tracings were definitely abnormal; one half of these were among patients over 50 years of age. Only 5 of 162 tracings in patients under 20 years of age were abnormal; one of these (incomplete right bundle branch block) might have mattered had the patient been considered for treatment with drugs that lengthen intraventricular conduction times, such as tricyclic antidepressants or thioridazine. CONCLUSION: Routine screening ECGs done on psychiatric patients yielded relatively few abnormalities except in those over the age of 50 years, confirming the experience with such surveys in the general population. The prevalence of abnormalities among these patients was frequent enough to merit routine screening. For other patients regardless of age, ECGs are indicated whenever a history or physical findings suggest cardiovascular disease or whenever it is proposed to treat these patients with psychotherapeutic drugs known to increase cardiac conduction times or otherwise alter cardiac function.

A day in the woods.

Through an outdoor "teams course," nurses can learn more effective interaction and problem-solving skills. The experience of four groups of intensive care unit nurses is described. Feedback and suggestions provide insights helpful in structuring similar experiences.

New psychotherapeutic drugs.

Many new psychotherapeutic drugs are being developed for the major clinical indications for which they might be useful. As usual, we hope not only to obtain better drugs but also to posit hypotheses based on the presumed mode of action of effective drugs. Thus, we have a chance to test the role of serotonin, via the 5HT1A receptor, in anxiety or to test the possible significance of multiple benzodiazepine receptors. Among antidepressant agents, we have a chance to determine the relative roles of norpinephrine and serotonin in the pathogenesis of these disorders. We may also determine whether antidepressant actions involve a number of aminergic neurotransmitters. Among antipsychotic drugs, the importance of dopamine D2 receptor blockade has diminished with the advent of atypical drugs affecting a variety of other receptors. It might also be possible to delineate more clearly the role of serotonin in psychosis. The GABA hypothesis of mania can be tested in a number of ways by current drugs. The role of calcium antagonism remains to be demonstrated. The acetylcholine hypothesis of Alzheimer's disease will be tested further by new compounds under trial. However, it seems increasingly doubtful that current drugs under test will explicate the current hypothesis of the abnormal processing of beta-amyloid precursor protein in that disorder. Thus, we hope, as we have for the past three decades, to be able to use drugs not only to treat, but also to generate hypotheses. It is a kind of bootstrapping enterprise, but our ultimate hope is not only to be better able to treat our patients, but also to better understand their afflictions.

Marijuana and immunity.

Despite the fairly large literature that developed during the past 15 years or so, the effect of cannabinoids on the immune system is still unsettled. The evidence has been contradictory and is more supportive of some degree of immunosuppression only when one considers in vitro studies. These have been seriously flawed by the very high concentrations of drug used to produce immunosuppression and by the lack of comparisons with other membrane-active drugs. The closer that experimental studies have been to actual clinical situations, the less compelling has been the evidence. Although the topic was of great interest during the 1970's, as indicated by the preponderance of the references from that period, interest has waned during the present decade. This waning of interest suggests that perhaps most investigators feel that this line of inquiry will not be rewarding. The AIDS epidemic has also diverted the attention of immunologists to the far more serious problem of the truly devastating effects a retrovirus can have on a portion of the immune system. The relationship between the use of social drugs and the development of clinical manifestations of AIDS has been of some interest, however. Persons infected with the virus but not diagnosed as AIDS have been told to avoid the use of marijuana and/or alcohol. This advice may be reasonable as a general health measure, but direct evidence that heeding this warning will prevent the ultimate damage to the immune system is totally lacking.