Delta-9-tetrahydrocannabinol as an antiemetic

The use of delta-9-tetrahydrocannabinol (THC) as an antiemetic in patients undergoing cancer chemotherapy is reviewed. The pharmacokinetics of THC is discussed, and the agent's effects on the central nervous, cardiovascular, respiratory, gastrointestinal, immune, endocrine, and reproductive systems are presented. The toxicology, potential hazards, and adverse reactions of THC are reviewed. Also reviewed are studies of THC's use as an antiemetic. THC appears to be an effective antiemetic in cancer patients undergoing chemotherapy. The maximal antinauseant effects often correlate with the attainment of a "high". THC has been found consistently more effective than placebo and at least as effective as prochlorperazine. In phenothiazine-resistant patients, THC's effectiveness has exceeded that of the phenothiazines. Efficacy may depend on the chemotherapeutic agent causing emesis. Elderly patients do not tolerate the THC "high" well. Concurrent administration of phenothiazines with THC may block the "high" without reducing THC's antiemetic effectiveness. Because of variations in individual tolerance, absorption, and the form of chemotherapy, flexibility is necessary in establishing the correct dose of THC.     

Using guiding-idea theories of the person to develop educational campaigns against drug abuse and other health-threatening behavior

Educational campaigns against health-threatening behaviors such as drug abuse may lose effectiveness because they tend to be narrow, atheoretical and to stress negative effects. As a corrective, it is proposed that health campaigns take into account the broad range of human needs and consider how the health-threatening behavior may be gratifying to each need. This allows taking into consideration not just the bad effects (which tend to be obvious) of such behaviors as drug abuse, but also the gratifications they provide to a variety of human needs, by their associated lifestyles as well as by their pharmaceutical effects. In this way anti-drug campaigns can be made to cope more relevantly with the attractions of such health-threatening behaviors. We sketch 16 theorized human needs, widely contrasting in their assumption of what instigates human action and what terminates it, each of which theories has proven provocative in guiding basic research. From each of the 16 theories some implications are drawn regarding the attractions of drug abuse and regarding the design of educational campaigns against such health-threatening behaviors.     

Cognitive, mood, and functional evaluations using touchscreen technology

We describe the design and development of the Cognitive Evaluation Protocol (CEP), a computer software program for evaluating cognitive and functional capacities and mood. The program is self-administered by subjects using touchscreen monitors for input. Stimuli in CEP subtests are randomized to reduce the effects of learning on repeated assessments. Findings demonstrate that a) minimum instruction is required for touchscreen use, even for computer-naive subjects; c) both normative subjects and psychiatric patients respond positively to self-administered evaluations; and c) CEP can be used for within-subject repeated evaluations with minimal distortion of results due to practice effects. The CEP Report Generator provides immediate printed performance results and creates a database for long-term digital storage and information use.     

Limited access trial using amifostine for protection against cisplatin- and three-hour paclitaxel-induced neurotoxicity: a phase II study of the Gynecologic Oncology Group.

PURPOSE: The purpose of this study was to determine whether amifostine (WR-2721) prevents or ameliorates clinically significant (grade 2 to 4) neurotoxicity associated with cisplatin and 3-hour paclitaxel chemotherapy.Materials and METHODS: The chemotherapy program consisted of intravenous paclitaxel 175 mg/m2 over 3 hours followed by amifostine 740 mg/m2 and cisplatin 75 mg/m2 administered over 90 minutes beginning 15 minutes after amifostine administration. At baseline, before each treatment cycle, and for 3 months after completing chemotherapy, patients were evaluated for evidence of neurotoxicity and other treatment-related adverse effects using three methods: standard clinical evaluation (National Cancer Institute common toxicity criteria [CTC] grading), a neurotoxicity questionnaire to assess symptoms and limitations imposed by peripheral neuropathy, and vibration perception threshold (VPT) testing. RESULTS: Four of 27 assessable patients developed grade 2 to 4 neurotoxicity based on clinical assessments and CTC grading. This number of neuropathic events exceeded the predetermined threshold level for a second stage of accrual and the study was closed. CONCLUSION: Amifostine's level of activity in this trial was insufficient to warrant further study in a phase III trial. Based on the receiver operating characteristic analysis, it would appear that VPT measurements are less sensitive to the development of peripheral neuropathy than the neurotoxicity questionnaire. The questionnaire, referred to as the Functional Assessment of Cancer Therapy/Gynecologic Oncology Group-Neurotoxicity, may be used instead of VPT measurements in future studies of chemotherapy-induced peripheral neuropathy.     

Inhibition of bone repair in a rat model for chronic and excessive alcohol consumption.

Alcohol abuse is associated with increases in both the incidence of fractures and complications in fracture healing. The purpose of this study was to determine the dose-dependent effects of ethanol on bone repair in a rat model. Three-month-old male Wistar rats were continuously fed liquid diets containing ethanol as either 36% or 26% of total calories or control diets for 6 weeks. Then, a bone repair model was created in all rats. Bone healing and liver metabolism were evaluated 7 weeks after bone injury. For each dose, there were three ethanol-feeding groups receiving (1) ethanol for 13 weeks, (2) control diet for 13 weeks (pair-fed), and (3) ethanol before bone injury and control diet (pair-fed) after injury. Another group was fed ethanol (36%) before injury and given control diet ad libitum after injury. There were also two nutritional controls consuming control diet and standard rat chow ad libitum for 13 weeks. Abnormal liver metabolism was evident at the higher ethanol dose - increases in cytochrome P4502E1 specific activity (5-fold; P < .01), triglyceride content (4-fold; P < .02), and liver weight (25%; P = .05) - compared with pair-fed controls. The higher dose of ethanol resulted in deficient bone repair when compared with rats receiving ethanol-free control diet by pair-feeding: 26% less (P = .02) rigidity of the repaired bone, 41% less (P = .02) intrinsic stiffness, 24% less intrinsic strength (P = .05), and 14% less (P = .001) ash density of the repair tissue. The reduced food consumption of ethanol-fed rats compared with that in the nutritional controls did not contribute to this deficiency. Furthermore, removal of ethanol (as 36% of calories) from the diet after bone injury completely restored normal bone healing and nearly normalized the liver metabolism. The lower ethanol dose (26% of calories) had a minimal effect on liver metabolism and bone repair. We conclude that ethanol (as 36% of calories) in the rat diet, especially during the postinjury period, was solely responsible for the observed inhibition of bone repair.     

Antiparkinsonian actions of ifenprodil in the MPTP-lesioned marmoset model of Parkinson's disease

Dopamine-replacement strategies form the basis of most symptomatic treatments for Parkinson's disease. However, since long-term dopamine-replacement therapies are characterized by many side effects, most notably dyskinesia, the concept of a nondopaminergic therapy for Parkinson's disease has attracted great interest. To date, it has proved difficult to devise a nondopaminergic therapy with efficacy comparable to that of dopamine replacement. In animal models of Parkinson's disease, loss of striatal dopamine leads to enhanced excitation of striatal NR2B-containing NMDA receptors. This is responsible, in part at least, for generating parkinsonian symptoms. Here we demonstrate that, in the MPTP-lesioned marmoset, monotherapy with the NR2B-selective NMDA receptor antagonist, ifenprodil, administered de novo, has antiparkinsonian effects equivalent to those of l-DOPA (administered as its methyl ester form). In MPTP-lesioned marmosets, median mobility scores, following vehicle-treatment were 12.5/h (range 6-21), compared to 61/h (range 26-121) in normal, non-MPTP-lesioned animals. Following ifenprodil (10 mg/kg) treatment in MPTP-lesioned marmosets, the median mobility score was 66/h (range 34-93), and following l-DOPA (10 mg/kg i.p.) treatment 89/h (range 82-92). The data support the proposal that NR2B-selective NMDA receptor antagonists have potential as a nondopaminergic monotherapy for the treatment of parkinsonian symptoms when given de novo.     

Reducing psychiatric hospitalization among mentally ill veterans living in board-and-care homes

OBJECTIVE: The effectiveness of a community-based case management program at the Veterans Affairs West Los Angeles Healthcare Center in reducing hospital readmission of mentally ill veterans living in privately operated board-and-care homes was evaluated. METHODS: A retrospective cohort design was used. The sample consisted of 321 patients identified by hospital records as living in one of 24 board-and-care homes in the Los Angeles area that were approved by the community residential care program. A total of 214 subjects who received monthly home visits from case managers (program group) were compared with 107 subjects who did not receive monthly home visits (comparison group). The median number of psychiatric bed-days used was calculated for the two years before and after follow-up. The number of days from the start of follow-up to the first psychiatric hospitalization was also calculated. RESULTS: Among subjects in the program group, the median number of psychiatric bed-days used decreased significantly, from 59 days to 50 days. No significant change in the median number was observed for comparison subjects. Comparison subjects were rehospitalized 1.7 times more often than program subjects. Overall, program subjects under age 62 (younger subjects) were rehospitalized 2.5 times more often than older subjects. In the program group, those who had received home visits for more than two years were hospitalized three times more often than those who had received visits for less than two years, and younger subjects were rehospitalized 1.8 times more often than older subjects. CONCLUSIONS: The findings suggest that home visits conducted by case managers in a community residential care program helped reduce psychiatric hospitalization among veteran patients living in privately operated board-and-care homes.     

Lexical retrieval during fluent speech production: an fMRI study

We investigated the neural correlates of lexical retrieval during fluent speech production using fMRI. Blood oxygenation level dependent (BOLD) contrast was measured while subjects spoke about 7 Rorschach inkblots for 3 min each. Varying degrees of speech rate were elicited during each run. In a within-subject design, the number of words produced was correlated with the BOLD contrast in the two runs in each subject that showed the highest variance of speech output. The rate of articulation was positively correlated with activation in the left superior temporal (BA 22) and supramarginal (BA 39/ 40) gyri. The main negative correlations were in the fusiform gyri bilaterally (BA 19), the posterior cingulate (BA 30) and superior occipital gyrus (BA 19). Lexical retrieval during continuous language production engages areas in the left temporal and inferior parietal cortex. This pattern of activation differs from that evident during the generation of single words (verbal fluency), which is more associated with left prefrontal activation.