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J Acquir Immune Defic Syndr. 2007 Jun 21;: 17589370 (P,S,G,E,B,D) Cited:2
From the *Division on Substance Abuse, New York State Psychiatric Institute, and Department of Psychiatry, College of Physicians and Surgeons of Columbia University, New York, NY; and †Department of Psychology, Columbia University, New York, NY.
OBJECTIVES::conditions Individuals with HIV constitute the largest group using cannabinoids for medicinal reasons; yet, no studies have directly compared the tolerability conditions and efficacy of smoked marijuana and oral dronabinol maintenance in HIV-positive marijuana smokers. This placebo-controlled within-subjects study evaluated marijuana and caloric dronabinol across a range of behaviors: eating topography, mood, cognitive performance, physiologic measures, and sleep. METHODS:: HIV-positive marijuana smokers (n smokers. = 10) completed 2 16-day inpatient phases. Each dronabinol (5 and 10 mg) and marijuana (2. % and 3.9% Delta-tetrahydrocannabinol [THC])10 dose was administered 4 times daily for 4 days, but only 1 drug was active per day, thereby maintaining double-blind and dosing. Four days of placebo washout separated each active cannabinoid condition. RESULTS:: As compared with placebo, marijuana and dronabinol dose was dependently increased daily caloric intake and body weight in HIV-positive marijuana smokers. All cannabinoid conditions produced significant intoxication, except for and low-dose dronabinol (5 mg); the intoxication was rated positively (eg,''good drug effect'') with little evidence of discomfort and no (3.9% impairment of cognitive performance. Effects of marijuana and dronabinol were comparable, except that only marijuana (3.9% THC) improved ratings of a sleep. CONCLUSIONS:: These data suggest that for HIV-positive marijuana smokers, both dronabinol (at doses 8 times current recommendations) and marijuana (3.9% were well tolerated and produced substantial and comparable increases in food intake.

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Exp Clin Psychopharmacol. 2009 Aug ;17 (4):217-25 19653787 (P,S,G,E,B,D)
Center for Alcohol and Addiction Studies.
Although were alcohol and nicotine administration studies have demonstrated that manipulating subjects' expectancies regarding drug content affects drug response, research with marijuana found has not adequately studied drug expectancy effects. The present pilot study was the first to evaluate the credibility and effect 20 of expectancy manipulation on subjective measures and smoking patterns using a marijuana administration balanced-placebo design (BPD). In a 2 x pilot 2 instructional set (told delta-9-tetrahydrocannabinol [THC] vs. told no THC) by drug (smoked marijuana with 2.8% THC vs. placebo) between-subjects delta-9-tetrahydrocannabinol design, the authors examined the effect of marijuana expectancy manipulation and the pharmacologic effect on affective and physiologic measures, cigarette studied ratings, and smoking behavior with 20 marijuana smokers (mean age = 20 years; 25% female). Large main effects of expectancy and were found on ratings of cigarette potency, strength, taste, smell, and satisfaction, and observed smoking behavior. Pharmacologic effects were particularly [THC] evident for self-reported physical reactions to marijuana and cigarette potency and satisfaction ratings. This study demonstrated the feasibility of the feasibility BPD research with marijuana and yielded promising results for future studies examining the independent and combined effects of marijuana pharmacology and and expectancies.(PsycINFO Database Record (c) 2009 APA, all rights reserved).
Addict Biol. 2008 Feb 14;: 18279497 (P,S,G,E,B,D) Cited:3
Division on Substance Abuse, New York State Psychiatric Institute and Department of Psychiatry, College of Physicians and Surgeons of Columbia University, USA.
Awareness as of cannabis dependence as a clinically relevant issue has grown in recent years. Clinical and laboratory studies demonstrate that chronic reward, marijuana smokers can experience withdrawal symptoms upon cessation of marijuana smoking and have difficulty abstaining from marijuana use. This paper the will review data implicating the cannabinoid CB1 receptor in regulating the behavioral effects of Delta(9)-tetrahydrocannobinol (THC), the primary psychoactive component smokers of cannabis, across a range of species. The behavioral effects that will be discussed include those that directly contribute to CB1 the maintenance of chronic marijuana smoking, such as reward, subjective effects, and the positive and negative reinforcing effects of marijuana,studies THC and synthetic cannabinoids. The role of the CB1 receptor in the development of marijuana dependence and expression of withdrawal reinforcing will also be discussed. Lastly, treatment options that may alleviate withdrawal symptoms and promote marijuana abstinence will be considered.

Other papers by authors:

Psychopharmacology (Berl). 2008 Dec 4;: 19052727 (P,S,G,E,B,D)
Department of Psychology, Columbia University, New York, USA.
RATIONALE:of Methamphetamine attenuates disruptions that occur after changes in work shifts. The reinforcing effects of the drug during shift work have mood, yet to be characterized. OBJECTIVES: This study examined methamphetamine-related mood, performance, and reinforcing effects during simulated shift work. MATERIALS AND an METHODS: Ten volunteers (four women and six men) completed this 19-day study. Participants were given an opportunity to self-administer oral AND methamphetamine (10 mg) or receive a $1 voucher before and after an 8-h work period for four consecutive days under in two shift conditions:(1)"day shift" in which they went to bed at 2400 hours and woke up at 0800 and hours and (2)"night shift" when they went to bed at 1600 hours and woke up at 2400 hours. Thus,significantly participants completed task batteries either from 0815 to 1715 hours or from 0015 to 0915 hours. Shift conditions alternated three they times during the study and were separated by an "off" day. RESULTS: Night-shift work disrupted psychomotor task performance and some 34%). ratings of mood, especially on the first night. Consistent with this, participants chose to take methamphetamine significantly more often on study. the first night-shift night compared with the first day-shift day. Regardless of shift condition, however, participants selected markedly more methamphetamine CONCLUSIONS: doses before the work period than after it (73% versus 34%). CONCLUSIONS: These data show that methamphetamine self-administration occurred more 34%). often before work rather than after work, suggesting that the use of stimulants by shift workers may be one strategy show employed to meet behavioral demands especially under conditions engendering poor performance, fatigue, and/or sleep disruptions.
Psychopharmacology (Berl). 2007 Dec 27;: 18161012 (P,S,G,E,B,D) Cited:1
INTRODUCTION:loss Individuals seeking treatment for their marijuana use rarely achieve sustained abstinence. OBJECTIVES: The objectives of the study are to determine associated if THC, a cannabinoid agonist, and lofexidine, an alpha(2)-adrenergic receptor agonist, given alone and in combination, decreased symptoms of marijuana intake, withdrawal and relapse, defined as a return to marijuana use after a period of abstinence. MATERIALS AND METHODS: Nontreatment-seeking, male of volunteers (n = 8), averaging 12 marijuana cigarettes/day, were maintained on each of four medication conditions for 7 days: placebo,mg/day), tetrahydrocannabinol (THC)(60 mg/day), lofexidine (2.4 mg/day), and THC (60 mg/day) combined with lofexidine (2.4 mg/day); each inpatient phase was agonist, separated by an outpatient washout phase. During the first three inpatient days, placebo marijuana was available for self-administration (withdrawal). For sleep the next 4 days, active marijuana was available for self-administration (relapse). Participants paid for self-administered marijuana using study earnings. Self-administration,(2.4 mood, task performance, food intake, and sleep were measured. RESULTS: THC reversed the anorexia and weight loss associated with marijuana produced withdrawal, and decreased a subset of withdrawal symptoms, but increased sleep onset latency, and did not decrease marijuana relapse. Lofexidine use was sedating, worsened abstinence-related anorexia, and did not robustly attenuate withdrawal, but improved sleep and decreased marijuana relapse. The combination produced of lofexidine and THC produced the most robust improvements in sleep and decreased marijuana withdrawal, craving, and relapse in daily THC marijuana smokers relative to either medication alone. CONCLUSIONS: These data suggest the combination of lofexidine and THC warrant further testing robust as a potential treatment for marijuana dependence.
Psychopharmacology (Berl). 2005 Aug ;181:170-8 15778874 (P,S,G,E,B)
RATIONALE:participants; No studies to date have directly compared the tolerability and efficacy of smoked marijuana and oral dronabinol in HIV(+) marijuana the smokers. OBJECTIVES: The aim of this study was to compare dronabinol ( , 10, 20, 30 mg p.o.) and marijuana [ . ,significant 1.8, 2.8, 3.9% Delta(9)-tetrahydrocannabinol (THC)] in two samples of HIV(+) marijuana smokers: those with (n=15) and those without (n=15) a marijuana clinically significant loss of muscle mass (<90% body cell mass/height), which is one component of AIDS wasting. METHODS: Mood, physical intake, symptoms, self-selected food intake, cardiovascular data, and cognitive task performance were measured before and repeatedly after dronabinol and marijuana administration dronabinol in eight 7-h sessions. Marijuana and dronabinol were administered in randomized order using a within-subject, staggered, double-dummy design. RESULTS: As of compared to placebo,(1) marijuana (1.8, 2.8, 3.9% THC) and the lower dronabinol doses (10, 20 mg) were well tolerated data, (e.g., few physical symptoms, significant increases in ratings of "good drug effect") in both groups of participants; the highest dose CONCLUSIONS: of dronabinol (30 mg) was poorly tolerated in a subset of participants;(2) marijuana and dronabinol significantly increased caloric intake HIV(+) in the low bioelectrical impedance analysis (BIA) group but not in the normal BIA group; and (3) drug effects on CONCLUSIONS: cognitive performance were minor. CONCLUSIONS: These data suggest that for experienced marijuana smokers with clinically significant muscle mass loss, both minor. dronabinol (at acute doses at least four to eight times the current recommendation) and marijuana produce substantial and comparable increases suggest in food intake without producing adverse effects.
Psychopharmacology (Berl). 2009 Oct 27;: 19859698 (P,S,G,E,B,D)
Division on Substance Abuse, New York State Psychiatric Institute, Department of Psychiatry, College of Physicians and Surgeons of Columbia University, 1051 Riverside Dr., Unit 120, New York, NY, 10032, USA, sdc10@columbia.edu.
RATIONALE:of Sex differences in the analgesic effects of mu-opioid agonists have been documented extensively in rodents and, to a lesser extent,morphine. in non-human primates. To date, there have been few experimental studies investigating this effect in humans, and the conclusions have and been equivocal. OBJECTIVES: The aims of the present study were to examine potential sex differences in the analgesic, subjective, performance,this and physiological effects of morphine in human research volunteers. METHODS: Using a double-blind outpatient procedure, the present study investigated the a effects of intramuscular morphine ( , 5, and 10 mg/70 kg, i.m.) in men (N = 8) and women (N =there 10). The primary dependent measure was analgesia, as assessed by the cold pressor and mechanical pressure tests. Secondary dependent measures morphine included subjective, performance, and physiological effects of morphine, as well as plasma levels of morphine. RESULTS: No differences in the double-blind analgesic and performance effects of morphine were observed between men and women, but significant differences in morphine's subjective effects were morphine found. Specifically, men reported greater positive effects, whereas women reported greater negative effects after morphine administration. CONCLUSIONS: These data suggest OBJECTIVES: that, in humans, there are sex differences in the subjective mood-altering effects of morphine but, based on this limited sample,morphine there is little evidence for sex differences in its analgesic effects.
Psychopharmacology (Berl). 2006 Sep 14;: 16972105 (P,S,G,E,B)
Division on Substance Abuse, New York State Psychiatric Institute and Department of Psychiatry, College of Physicians and Surgeons, Columbia University, 1051 Riverside Drive, Unit 120, New York, NY, 10032, USA, sdc10@columbia.edu.
RATIONALE:given Naltrexone is an opioid antagonist that is currently approved as a treatment for opioid and alcohol dependence. Although it is the highly effective in completely antagonizing the effects of opioids, medication noncompliance is a difficult obstacle to treatment. Therefore, a sustained-release measured form of naltrexone may improve treatment outcome. OBJECTIVE: The present study was designed to evaluate the time course, safety, and improve effectiveness of a depot formulation of naltrexone (Depotrex((R))). MATERIALS AND METHODS: Five heroin-dependent individuals participated in an 8-week inpatient study.12.5, After a 1-week detoxification period, the effects of a range of heroin doses ( , 6.25, 12.5, and 25 mg, i.v.)obstacle were examined. Participants then received 384 mg naltrexone base. The effects of heroin were again evaluated for the next 6 ratio weeks. One dose of heroin was tested per day and the entire dose range was tested each week. Doses were 25 administered in non-systematic order. During a morning sample session, participants received a dose of heroin and $20 and subjective, performance,mean and physiological effects were measured both before and after drug administration. During an afternoon choice session, participants were given the time opportunity to choose the sampled heroin dose and/or amount of money using a modified progressive ratio procedure. RESULTS: Depot naltrexone mean antagonized both the reinforcing and subjective effects of heroin for 4-5 weeks. Subjective ratings of withdrawal were reduced after week on 2 and throughout the remainder of the study. The effects of heroin on mean trough pupil diameter began to emerge began by week 5. There were no clinically significant effects on respiratory or cardiovascular function. CONCLUSIONS: The present results extend our for previous findings by showing that the reinforcing effects of heroin were reduced for 4-5 weeks after administration of 384 mg examined. depot naltrexone.
Neuropsychopharmacology. 2005 Dec 14;: 16395298 (P,S,G,E,B,D) Cited:7
[1] 1Department of Psychiatry, Division on Substance Abuse, New York State Psychiatric Institute, College of Physicians and Surgeons of Columbia University, New York, NY, USA [2] 2Department of Psychology, Columbia University, New York, NY, USA.
Common a complaints among shift workers are sleep disruptions and increased sleepiness while working, which may contribute to shift workers being more a susceptible to diminished performance and work-related accidents. The purpose of this double-blind, within-participant study was to examine the effects of shift. the alerting agent modafinil on cognitive/psychomotor performance, mood, and measures of sleep during simulated shift work. In all, 11 participants to completed this 23-day residential laboratory study. They received a single oral modafinil dose ( , 200, 400 mg) 1 h after mg) waking for three consecutive days under two shift conditions: day shift and night shift. Shifts alternated three times during the The study, and shift conditions were separated by an 'off' day. When participants received placebo, cognitive performance and subjective ratings of night mood were disrupted during the night shift, relative to the day shift. Objective and subjective measures of sleep were also h disrupted, but to a lesser extent. Modafinil reversed disruptions in cognitive performance and mood during the night shift. While modafinil shift produced few effects on sleep measures during the night shift, the largest dose produced several sleep alterations during the day cognitive/psychomotor shift. These data demonstrate that abrupt shift changes produced cognitive performance impairments and mood disruptions during night shift work. Therapeutic changes doses of modafinil attenuated night-shift-associated disruptions, but the larger dose produced some sleep impairments when administered during day-shift work.Neuropsychopharmacology advance shift online publication, 14 December 2005; doi:10.1038/sj.npp.1300991.
Drug Alcohol Depend. 2005 Oct 1;80 (1):53-61 16157231 (P,S,G,E,B,D) Cited:7
Division on Substance Abuse, Department of Psychiatry, College of Physicians and Surgeons of Columbia University, New York, NY, USA. mh235@columbia.edu
Gamma-aminobutyric mg), acid (GABA) agonists, such as the GABA analogue, gabapentin, may provide new avenues for pharmacological treatment of cocaine dependence. The mg), purpose of this study was to develop a smoked cocaine drug discrimination procedure in humans to test the effects of mg), gabapentin maintenance on the discriminative stimulus, subjective, cognitive and cardiovascular effects of smoked cocaine. Eight male, nontreatment-seeking, cocaine-dependent volunteers, residing to on an inpatient research unit for 47 days completed a within-subjects, counter-balanced design. Participants learned to discriminate between cocaine (25 discriminate mg) and placebo, and once the criterion for discrimination was met, smoked cocaine dose-effect functions ( , 6, 12, 25 and a 50 mg) were determined under three gabapentin maintenance conditions ( , 600 and 1200 mg/day po). The highest dose of gabapentin Gabapentin tested (1200 mg/day) decreased the discriminative stimulus effects of cocaine (6 mg), decreased cocaine craving by 41-53% following cocaine administration cocaine (6 and 12 mg), and increased heart rate following either placebo or cocaine (12 mg) administration. Gabapentin did not significantly in affect psychomotor task performance or the subjective effects of cocaine. Although the direction of gabapentin's effects was appropriate for a stimulus, potential treatment medication, i.e., a decrease in cocaine-elicited craving and a decrease in cocaine's discriminative stimulus effects, these effects were cocaine-elicited limited to low doses of cocaine. The results suggest gabapentin may not produce effects sufficiently robust to be clinically useful,in at least at this dose regimen.
Psychopharmacology (Berl). 2009 Nov 17;: 19916063 (P,S,G,E,B,D)
Division of Substance Abuse, New York State Psychiatric Institute, 1051 Riverside Dr., Unit 120, New York, NY, 10032, USA.
RATIONALE:and Most reports of the effects of methamphetamine and 3,4-methylenedioxymethamphetamine (MDMA) on speech have been anecdotal. OBJECTIVES: The current study used the a within-participant design to assess the effects of methamphetamine and MDMA on speech. MATERIALS AND METHODS: Eleven recreational users of listened amphetamines completed this inpatient, within-participant, double-blind study, during which they received placebo, methamphetamine (20, 40 mg), and MDMA (100 mg)speech. on separate days. Following drug administration, study participants described movies viewed the previous evening and completed mood scales. RESULTS: Methamphetamine viewed increased quantity of speech, fluency, and self-ratings of talkativeness and alertness, while it decreased the average duration of nonjuncture unfilled the pauses. MDMA decreased fluency and increased self-ratings of inability to concentrate. To determine if methamphetamine- and MDMA-related effects were perceptible,coherent undergraduates listened to the participants' movie descriptions and rated their coherence and the speaker's mood. Following methamphetamine, descriptions were judged the to be more coherent and focused than they were following MDMA. CONCLUSIONS: Methamphetamine improved verbal fluency and MDMA adversely affected drugs fluency. This pattern of effects is consistent with the effects of these drugs on functioning in other cognitive domains. In completed general, methamphetamine effects on speech were inconsistent with effects popularly attributed to this drug, while MDMA-related effects were in agreement drugs with some anecdotal reports and discordant with others.
Biol Psychiatry. 2009 Oct 19;: 19846066 (P,S,G,E,B,D)
College of Physicians and Surgeons of Columbia University, New York, New York; Department of Psychiatry, New York State Psychiatric Institute, New York, New York.
BACKGROUND:(within Rates of relapse among cocaine-dependent patients are high, and new treatment approaches are needed. Clinical data demonstrate that a cocaine 4 vaccine (TA-CD) produces selective anticocaine antibodies, yet the impact of these antibodies on cocaine's direct effects is unknown. The objective Those of this human laboratory study was to measure the relationship between antibody titers and the effects of smoked cocaine on unknown. ratings of intoxication, craving, and cardiovascular effects. METHODS: Ten cocaine-dependent men not seeking drug treatment spent 2 nights per week 13 for 13 weeks inpatient where the effects of cocaine ( mg, 25 mg, 50 mg) were determined before vaccination and of at weekly intervals thereafter. Two doses of TA-CD (82 mug, n = 4; 360 mug, n = 6) were administered drug at weeks 1, 3, 5, and 9. RESULTS: Peak plasma antibody levels, which were highly variable, significantly predicted cocaine's effects.inpatient Those individuals in the upper half of antibody production had an immediate (within 4 minutes of cocaine smoking) and robust (p (55%-81%) reduction in ratings of good drug effect and cocaine quality, while those in the lower half showed only a the nonsignificant attenuation (6%-26%). Self-reported cocaine use while participants were outpatient tended to decrease as a function of antibody titer (p (p <.12). By contrast, higher antibody levels predicted significantly greater cocaine-induced tachycardia. CONCLUSIONS: The TA-CD vaccine substantially decreased smoked cocaine's titer intoxicating effects in those generating sufficient antibody. These data support further testing of cocaine immunotherapy as a treatment for cocaine By dependence.
Drug Alcohol Depend. 2009 Sep 22;: 19783386 (P,S,G,E,B,D)
College of Physicians and Surgeons of Columbia University, New York State Psychiatric Institute, New York, NY 10032, United States.
The block. purpose of this double-blind, randomized, outpatient study was to evaluate the reinforcing and subjective effects of modafinil (200, 400, or block. 600mg) in cocaine abusers. Twelve participants (2 female, 10 male) completed this study, consisting of 3 blocks of 7 sessions;the each block tested a difference dose of modafinil. During the first 2 sessions of each block, participants "sampled" 1 of or the doses of modafinil, and placebo. These doses of modafinil and placebo were available for the subsequent five choice sessions a of the block. In each choice session, participants had an opportunity to administer active or placebo capsules. Modafinil administration did of not differ from placebo administration, and subjective-effects ratings were not systematically altered as a function of modafinil dose. Results suggest an that modafinil does not have abuse liability in cocaine abusers.

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Neuropsychobiology. 2009 Sep 21;60 (2):94-103 19776653 (P,S,G,E,B,D)
Department of Psychiatry, University Hospital of Zurich, Zurich, Switzerland.
Background:significantly Cannabis is one of the most commonly used illicit drugs. Reduced neural and behavioral reactions to reward have been demonstrated worse in other forms of addiction, as expressed by reduced mood reactivity and lack of striatal activation to rewards, but this mood effect has not yet been investigated in cannabis users. Methods: We hypothesized that cannabis users and tobacco smokers would evidence but lower positive mood ratings in rewarded conditions than control participants and that this reduction would be greater in cannabis users examined than in smokers. We examined the influence of reward on mood and performance in a group of regular cannabis users,reactivity a group of tobacco smokers and a group of nonsmokers while they performed a spatial recognition task with delayed response A that incorporated 3 levels of difficulty. Correct responses were either not reinforced or reinforced with money. We measured the accuracy influence of reactions, reaction times and mood ratings throughout the trials. Results: Cannabis users rated their mood as significantly worse than Conclusions: the smokers and nonsmokers during the easiest level of the rewarded condition. A significant positive correlation between mood ratings and Methods: monetary reward was found in the nonsmokers but not in the cannabis users and smokers. The groups did not differ Our with regard to task performance. Conclusions: Our results suggest that regular cannabis use affects certain aspects of motivation and that Conclusions: both tobacco smoking and cannabis use lead to similar motivational changes. However, the use of cannabis seems to affect motivation that in a stronger way than does tobacco smoking alone.
Drug Alcohol Depend. 2009 May 13;: 19443132 (P,S,G,E,B,D)
Division on Substance Abuse, New York Psychiatric Institute and Department of Psychiatry, College of Physicians and Surgeons of Columbia University, 1051 Riverside Drive, Unit 120, New York, NY 10032, USA.
Recent points increases in marijuana smoking among the young adult population have been accompanied by the popularization of smoking marijuana as blunts for instead of as joints. Blunts consist of marijuana wrapped in tobacco leaves, whereas joints consist of marijuana wrapped in cigarette effects paper. To date, the effects of marijuana smoked as joints and blunts have not been systematically compared. The current within-subject,marijuana randomized, double-blind, placebo-controlled study sought to directly compare the subjective, physiological, and pharmacokinetic effects of marijuana smoked by these two these methods. Marijuana blunt smokers (12 women and 12 men) were recruited and participated in a 6-session outpatient study. Participants were wrapped blindfolded and smoked three puffs from either a blunt or a joint containing marijuana with varying Delta(9)-tetrahydrocannabinol (THC) concentrations ( . ,ratings 1.8, and 3.6%). Subjective, physiological (heart rate, blood pressure, and carbon monoxide levels) and pharmacokinetic effects (plasma THC concentration) were methods. monitored before and at specified time points for 3h after smoking. Joints produced greater increases in plasma THC and subjective carbon ratings of marijuana intoxication, strength, and quality compared to blunts, and these effects were more pronounced in women compared to marijuana men. However, blunts produced equivalent increases in heart rate and higher carbon monoxide levels than joints, despite producing lower levels monoxide of plasma THC. These findings demonstrate that smoking marijuana in a tobacco leaf may increase the risks of marijuana use carbon by enhancing carbon monoxide exposure and increasing heart rate compared to joints.
J Clin Psychopharmacol. 2009 Jun ;29 (3):255-8 19440079 (P,S,G,E,B,D)
Rockland Psychiatric Center, Orangeburg, NY 10962, USA. gs2272@columbia.edu
We There are reporting improvement of symptoms of schizophrenia in a small group of patients who received the cannabinoid agonist dronabinol (synthetic There Delta-9-tetrahydrocannabinol). Before this report, cannabinoids had usually been associated with worsening of psychotic symptoms. In a heuristic, compassionate use study,4 we found that 4 of 6 treatment-refractory patients with severe chronic schizophrenia but who had a self-reported history of improving Before with marijuana abuse improved with dronabinol. This improvement seems to have been a reduction of core psychotic symptoms in 3 patients of the 4 responders and not just nonspecific calming. There were no clinically significant adverse effects. These results complement the cannabinoid recent finding that the cannabinoid blocker rimonabant does not improve schizophrenic symptoms and suggest that the role of cannabinoids in results psychosis may be more complex than previously thought. They open a possible new role for cannabinoids in the treatment of with schizophrenia.
Psychol Med. 2009 Apr 1;:1-10 19335936 (P,S,G,E,B)
Institute of Psychiatry, The Biomedical Research Centre, King's College London, UK.
BACKGROUND:min Recent work suggests that heavy use of cannabis is associated with an increased risk of schizophrenia-like psychosis. However, there is of a dearth of experimental studies of the effects of the constituents of cannabis, such as Delta9-tetrahydrocannabinol (THC). In a study Task of intravenous (i.v.) synthetic THC in healthy humans, we aimed to study the relationship of the psychotic symptoms induced by of THC to the consequent anxiety and neuropsychological impairment.MethodTwenty-two healthy adult males aged 28+/-6 years (mean+/-s.d.) participated in experimental sessions in placebo-controlled which i.v. THC (2.5 mg) was administered under double-blind, placebo-controlled conditions. Self-rated and investigator-rated measurements of mood and psychosis [the of University of Wales Institute of Science and Technology Mood Adjective Checklist (UMACL), the Positive and Negative Syndrome Scale (PANSS) and highly the Community Assessment of Psychic Experiences (CAPE)] were made at baseline and at 30, 80 and 120 min post-injection. Participants conditions. also completed a series of neuropsychological tests [the Rey Auditory Verbal Learning Task (RAVLT), Digit Span, Verbal Fluency and the relationship Baddeley Reasoning Task] within 45 min of injection. RESULTS: THC-induced positive psychotic symptoms, and participant- and investigator-rated measurements of these the were highly correlated. Participants showed an increase in anxiety ratings but there was no relationship between either self- or investigator-rated between positive psychotic symptoms and anxiety. THC also impaired neuropsychological performance but once again there was no relationship between THC-induced positive no psychotic symptoms and deficits in working memory/executive function. CONCLUSIONS: These findings confirm that THC can induce a transient, acute psychotic psychotic reaction in psychiatrically well individuals. The extent of the psychotic reaction was not related to the degree of anxiety or Mood cognitive impairment.
Ann Pharm Fr. 2008 Aug ;66 (4):232-44 18847571 (P,S,G,E,B,D)
Laboratoire de pharmacocinétique et de toxicologie cliniques, groupe hospitalier du Havre, BP 24, 76083 Le Havre cedex, France. jgoulle@ch-havre.fr
Delta-9-tetrahydrocannabinol blood (Delta-9-THC) is the main psychoactive ingredient of cannabis. Smoking is currently most common use of cannabis. The present review focuses level on the pharmacokinetics of THC. The variability of THC in plant material which has significantly increased in recent years leads storage to variability in tissue THC levels from smoking, which is, in itself, a highly individual process. This variability of THC has content has an important impact on drug pharmacokinetics and pharmacology. After smoking THC bioavailability averages 30%. With a 3.55% THC THC cigarette, a peak plasma level near 160 ng/mL occurs approximately 10 min after inhalation. THC is eliminated quickly from plasma The in a multiphasic manner and is widely distributed to tissues, which is responsible for its pharmacologic effects. Body fat then 11-hydroxy serves as a long-term storage site. This particular pharmacokinetics explains the noncorrelation between THC blood level and clinical effects as bioavailability is observed for ethanol. A major active 11-hydroxy metabolite is formed after both inhalation and oral dosing (20 and 100%feces of parent, respectively). The elimination of THC and its many metabolites, mainly THC-COOH, occurs via the feces and urine for in several weeks. Thus, to confirm abstinence, urine THC-COOH analysis would be a useful tool. A positive result could be checked feces by gas chromatography-mass spectrometry THC blood analysis, indicative of a recent cannabis exposure.
Psychopharmacology (Berl). 2007 Dec 27;: 18161012 (P,S,G,E,B,D) Cited:1
INTRODUCTION:loss Individuals seeking treatment for their marijuana use rarely achieve sustained abstinence. OBJECTIVES: The objectives of the study are to determine associated if THC, a cannabinoid agonist, and lofexidine, an alpha(2)-adrenergic receptor agonist, given alone and in combination, decreased symptoms of marijuana intake, withdrawal and relapse, defined as a return to marijuana use after a period of abstinence. MATERIALS AND METHODS: Nontreatment-seeking, male of volunteers (n = 8), averaging 12 marijuana cigarettes/day, were maintained on each of four medication conditions for 7 days: placebo,mg/day), tetrahydrocannabinol (THC)(60 mg/day), lofexidine (2.4 mg/day), and THC (60 mg/day) combined with lofexidine (2.4 mg/day); each inpatient phase was agonist, separated by an outpatient washout phase. During the first three inpatient days, placebo marijuana was available for self-administration (withdrawal). For sleep the next 4 days, active marijuana was available for self-administration (relapse). Participants paid for self-administered marijuana using study earnings. Self-administration,(2.4 mood, task performance, food intake, and sleep were measured. RESULTS: THC reversed the anorexia and weight loss associated with marijuana produced withdrawal, and decreased a subset of withdrawal symptoms, but increased sleep onset latency, and did not decrease marijuana relapse. Lofexidine use was sedating, worsened abstinence-related anorexia, and did not robustly attenuate withdrawal, but improved sleep and decreased marijuana relapse. The combination produced of lofexidine and THC produced the most robust improvements in sleep and decreased marijuana withdrawal, craving, and relapse in daily THC marijuana smokers relative to either medication alone. CONCLUSIONS: These data suggest the combination of lofexidine and THC warrant further testing robust as a potential treatment for marijuana dependence.
AIDS Policy Law. 2007 Jun 15;22 (12):8 17642087 (P,S,G,E,B)
J Acquir Immune Defic Syndr. 2007 Jun 21;: 17589370 (P,S,G,E,B,D) Cited:2
From the *Division on Substance Abuse, New York State Psychiatric Institute, and Department of Psychiatry, College of Physicians and Surgeons of Columbia University, New York, NY; and †Department of Psychology, Columbia University, New York, NY.
OBJECTIVES::conditions Individuals with HIV constitute the largest group using cannabinoids for medicinal reasons; yet, no studies have directly compared the tolerability conditions and efficacy of smoked marijuana and oral dronabinol maintenance in HIV-positive marijuana smokers. This placebo-controlled within-subjects study evaluated marijuana and caloric dronabinol across a range of behaviors: eating topography, mood, cognitive performance, physiologic measures, and sleep. METHODS:: HIV-positive marijuana smokers (n smokers. = 10) completed 2 16-day inpatient phases. Each dronabinol (5 and 10 mg) and marijuana (2. % and 3.9% Delta-tetrahydrocannabinol [THC])10 dose was administered 4 times daily for 4 days, but only 1 drug was active per day, thereby maintaining double-blind and dosing. Four days of placebo washout separated each active cannabinoid condition. RESULTS:: As compared with placebo, marijuana and dronabinol dose was dependently increased daily caloric intake and body weight in HIV-positive marijuana smokers. All cannabinoid conditions produced significant intoxication, except for and low-dose dronabinol (5 mg); the intoxication was rated positively (eg,''good drug effect'') with little evidence of discomfort and no (3.9% impairment of cognitive performance. Effects of marijuana and dronabinol were comparable, except that only marijuana (3.9% THC) improved ratings of a sleep. CONCLUSIONS:: These data suggest that for HIV-positive marijuana smokers, both dronabinol (at doses 8 times current recommendations) and marijuana (3.9% were well tolerated and produced substantial and comparable increases in food intake.
J Clin Exp Neuropsychol. 2007 May ;29 (4):357-64 17497559 (P,S,G,E,B)
Division on Substance Abuse, New York State Psychiatric Institute and Department of Psychiatry, College of Physicians and Surgeons of Columbia University. New York, NY. USA.
The Delta9-THC). impact of regular marijuana use on executive cognitive abilities, including decision making, is not well understood. While cross-sectional studies have Delta9-THC). suggested that substance abusers exhibit impaired decision making, as assessed by the Iowa Gambling Task, the direct role of marijuana after use in the Gambling Task performance of marijuana smokers has not been well defined. In this report, we present data by on performance on a modified Gambling Task in experienced marijuana users after they had smoked marijuana under controlled laboratory conditions.in A total of 36 marijuana users, who reported smoking approximately 24 marijuana cigarettes per week, completed this 3-session outpatient study.abusers During each session, these volunteers completed the Gambling Task once at baseline and 3 times after smoking a single marijuana sequence cigarette ( . , 1.8, or 3.9% Delta9-THC). Marijuana cigarettes were administered in a double-blind fashion, and the sequence of Delta9-THC concentration experienced was balanced across volunteers. Marijuana increased the time required to complete the task. However, advantageous card selection and money earned were on the task were not disrupted by marijuana. These data are consistent with previous findings that indicated that speed of marijuana performance on tests of executive function, but not accuracy, is disrupted in experienced marijuana users during marijuana intoxication.
Curr Med Res Opin. 2007 Mar ;23 (3):533-43 17355735 (P,S,G,E,B)
Bethesda Memorial Hospital, Comprehensive Cancer Care Center, Boynton Beach, FL 33435-7995, USA. mdeyal@hotmail.com
OBJECTIVE:combination To compare the efficacy and tolerability of dronabinol, ondansetron, or the combination for delayed chemotherapy-induced nausea and vomiting (CINV) in combination a 5-day, double-blind, placebo-controlled study. RESEARCH DESIGN AND METHODS: Patients receiving moderately to highly emetogenic chemotherapy received dexamethasone (20 mg 61 PO), ondansetron (16 mg IV) and either placebo or dronabinol (2.5 mg) prechemotherapy on day 1. Patients randomized to active mg treatment (dronabinol and/or ondansetron) also received dronabinol (2.5 mg) after chemotherapy on day 1. On day 2, fixed doses of mg), placebo, dronabinol (10 mg), ondansetron (16 mg), or combination therapy were administered. On days 3-5, patients received placebo, flexible doses moderately of dronabinol (10-20 mg), ondansetron (8-16 mg), or dronabinol and ondansetron (10-20 mg dronabinol, 8-16 mg ondansetron). MAIN OUTCOME MEASURES:(dronabinol, Total response (TR = nausea intensity <5 mm on visual analog scale, no vomiting/retching, no rescue antiemetic), nausea (occurrence and combination intensity) and vomiting/retching episodes. RESULTS: Sixty-four patients were randomized; 61 analyzed for efficacy. TR was similar with dronabinol (54%), ondansetron low (58%), and combination therapy (47%) versus placebo (20%). Nausea absence was significantly greater in active treatment groups (dronabinol, 71%; ondansetron,mg) 64%; combination therapy, 53%) versus placebo (15%; p < .05 vs. placebo for all). Nausea intensity and vomiting/retching were lowest number in patients treated with dronabinol. Active treatments were well tolerated. The low number of patients due to slow enrollment limits The the interpretation of these data. CONCLUSIONS: Dronabinol or ondansetron was similarly effective for the treatment of CINV. Combination therapy with due dronabinol and ondansetron was not more effective than either agent alone. Active treatments were well tolerated.
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