Papers by Matthew Baggott
Journal of psychopharmacology (Oxford, England), 2015
±3,4-methylenedioxymethamphetamine (MDMA) is widely believed to increase sociability. The drug al... more ±3,4-methylenedioxymethamphetamine (MDMA) is widely believed to increase sociability. The drug alters speech production and fluency, and may influence speech content. Here, we investigated the effect of MDMA on speech content, which may reveal how this drug affects social interactions. Thirty-five healthy volunteers with prior MDMA experience completed this two-session, within-subjects, double-blind study during which they received 1.5 mg/kg oral MDMA and placebo. Participants completed a five-minute standardized talking task during which they discussed a close personal relationship (e.g. a friend or family member) with a research assistant. The conversations were analyzed for selected content categories (e.g. words pertaining to affect, social interaction, and cognition), using both a standard dictionary method (Pennebaker's Linguistic Inquiry and Word Count: LIWC) and a machine learning method using random forest classifiers. Both analytic methods revealed that MDMA altered sp...
Efficacy, safety, and ethics of cosmetic neurology far from settled
Clinical pharmacology and therapeutics, 2010
In this issue, Larriviere and colleagues discuss the emerging use of drugs to enhance cognitive f... more In this issue, Larriviere and colleagues discuss the emerging use of drugs to enhance cognitive function. Several cautions they raise warrant amplification. People have tried to pharmacologically improve cognitive function for millennia, but Larriviere and colleagues postulate that new, more effective drugs will lead to the emergence of "cosmetic neurology." The ethics of using drugs to improve performance, as opposed to treating disease or restoring normal function, are far from settled.
Buprenorphine and naloxone interactions in opiate-dependent volunteers*
Clinical Pharmacology & Therapeutics, 1996
Sublingual buprenorphine appears useful in the treatment of opiate dependence. A combination subl... more Sublingual buprenorphine appears useful in the treatment of opiate dependence. A combination sublingual dose of buprenorphine and naloxone could have less potential for parenteral use by opiate-dependent individuals. To estimate the abuse potential of a combination formulation, we assessed the parenteral effects of a buprenorphine and naloxone combination in untreated heroin addicts. Eight healthy, opiate-dependent daily users of heroin were given, under double-blind conditions on four separate occasions, either (1) 2 mg buprenorphine, (2) 2 mg naloxone, (3) 2 mg buprenorphine and 2 mg naloxone combined, or (4) placebo as a single intravenous infusion during a 30-second interval. Opiate agonist and antagonist physiologic and subjective effects were measured. Data were analyzed by analysis of variance. Buprenorphine increased opiate intoxication and relieved withdrawal. The buprenorphine and naloxone combination precipitated opiate withdrawal and was unpleasant and dysphoric in all subjects. Fifty percent of the subjects were unable to distinguish between naloxone alone and the combined medications during the first hour of testing. The buprenorphine and naloxone combination has a low abuse potential in opiate-dependent daily heroin users.
Therapeutic Drug Monitoring, 2010
All addictive drugs produce tolerance and addicts compensate by increasing drug exposure. Thus, t... more All addictive drugs produce tolerance and addicts compensate by increasing drug exposure. Thus, the quantity of illicit drug ingested is related to the severity of addiction. Unfortunately, there are no objective methods to estimate intake for most addictive drugs. Using experimenteradministered doses of deuterium-labeled R-methamphetamine (R-[−]-MA-d3), we have developed a method to estimate the amount of abused methamphetamine intake in addicts enrolled in clinical trials. This study assessed the pharmacokinetics, pharmacodynamics, and tolerability of single oral doses of R-MA in healthy adults to select a dose of R-MA-d3 to be used as a biomarker for estimation the amount of methamphetamine abuse. This was a five-session randomized, doubleblind, placebo-controlled, balanced crossover study in eight subjects. Oral R-(−)-MA was dosed at 0 mg, 1 mg, 2.5 mg, 5 mg, or 10 mg; bioavailability was estimated by slow intravenous dosing (30 minutes) of 2.5 mg R-(−)-MA-d3 given with the 2.5 mg R-(−)-MA oral dose condition. Pharmacokinetic and pharmacodynamic measures were obtained. No serious adverse events occurred during the study and all doses of R-MA were well tolerated. Linear pharmacokinetics was observed within our oral dose range of 1 to 10 mg. Complete bioavailability and pharmacologic inactivity were found for all oral doses. These characteristics indicate the advantage of using a small oral R-(−)-MA-d3 dose as a biomarker to estimate exposure to abused methamphetamine. Based on these results, 5 mg R-(−)-MA-d3 has been selected as the biomarker dose in future studies. Preliminary findings from our study indicate that experimenteradministered oral R-(−)-MA-d3 may allow estimation of abused methamphetamine intake and exposure. Knowledge of the quantity of methamphetamine intake may allow better estimation of disease severity and treatment efficacy. Experience gained from this study also can be applied to the management of other drug dependence problems such as cocaine, cannabinoid, and opiate addiction.
Substance Abuse: Research and Treatment, 2010
Patients treated for methamphetamine (MA) dependence have a high rate of relapse, and stress is t... more Patients treated for methamphetamine (MA) dependence have a high rate of relapse, and stress is thought to play a key role. We sought to develop a computerized procedure for experimentally inducing stress in MA users. In a within-subjects design, we compared a computerized subtraction stress task (SST) to personalized stress-imagery scripts and a control condition (neutral imagery) in 9 former MA users, recruited in San Francisco in 2006-2007. We assessed blood hormone levels, anxiety and craving for MA on visual analog scales, and the Positive and Negative Affect Schedule and made linear mixed-effects models to analyze the results. Both the SST and stress scripts were effective in inducing self-report markers of stress in MA users. Because the SST is easily reproducible and requires less time of staff and participants, it may be a useful alternative for measuring stress reactivity in drug users.
Psychopharmacology, 2002
Rationale: 3,4-Methylenedioxymethamphetamine (MDMA) is a widely used phenethylamine. Reports have... more Rationale: 3,4-Methylenedioxymethamphetamine (MDMA) is a widely used phenethylamine. Reports have described the effects of MDMA in a controlled laboratory setting, but the full range of effects of MDMA in humans is still not completely characterized. Objectives: To describe the physiological, subjective, and hormonal changes after single doses of MDMA in a laboratory setting and examine relationships between these effects. Methods: Eight MDMA-experienced volunteers each received placebo, 0.5 mg/kg, and 1.5 mg/kg oral doses of MDMA in a double-blind crossover study. Results: The 1.5 mg/kg dose (comparable to that typically used by most participants) produced significant subjective effects, peaking at about 2 h after dosing, including some effects commonly associated with stimulant drugs, hallucinogens, and entactogens. MDMA significantly increased plasma cortisol, prolactin, and dehydroepiandrosterone (DHEA) levels. Increase in plasma cortisol after the 1.5 mg/kg dose correlated with increased heart rate, rate-pressure product, and drug liking. Rise in DHEA correlated with euphoria. Conclusions: A typically used dose of MDMA produced effects commonly associated with stimulants and hallucinogens. Subjects liked MDMA. Correlations between cortisol and DHEA levels and some physiological and psychological effects are consistent with animal data suggesting that hormones modulate some responses to drugs of abuse.
Buprenorphine and naloxone combinations: the effects of three dose ratios in morphine-stabilized, opiate-dependent volunteers
Psychopharmacology, 1999
Sublingual buprenorphine is a promising new treatment for opiate dependence, but its opioid agoni... more Sublingual buprenorphine is a promising new treatment for opiate dependence, but its opioid agonist effects pose a risk for parenteral abuse. A formulation combining buprenorphine with the opiate antagonist naloxone could discourage such abuse. The effects of three intravenous (IV) buprenorphine and naloxone combinations on agonist effects and withdrawal signs and symptoms were examined in 12 opiate-dependent subjects. Following stabilization on a daily dose of 60 mg morphine intramuscularly, subjects were challenged with IV doses of buprenorphine alone (2 mg) or in combination with naloxone in ratios of 2:1, 4:1, and 8:1 (1, 0.5, or 0.25 mg naloxone), morphine alone (15 mg) or placebo. Buprenorphine alone did not precipitate withdrawal and had agonist effects similar to morphine. A naloxone dose-dependent increase in opiate withdrawal signs and symptoms and a decrease in opioid agonist effects occurred after all drug combinations. Buprenorphine with naloxone in ratios of 2:1 and 4:1 produced moderate to high increases in global opiate withdrawal, bad drug effect, and sickness. These dose ratios also decreased the pleasurable effects and estimated street value of buprenorphine, thereby suggesting a low abuse liability. The dose ratio of 8:1 produced only mild withdrawal symptoms. Dose combinations at 2:1 and 4:1 ratios may be useful in treating opiate dependence.
Psychopharmacology of theobromine in healthy volunteers
Psychopharmacology, 2013
Theobromine, a methylxanthine related to caffeine and present in high levels in cocoa, may contri... more Theobromine, a methylxanthine related to caffeine and present in high levels in cocoa, may contribute to the appeal of chocolate. However, current evidence for this is limited. We conducted a within-subjects placebo-controlled study of a wide range of oral theobromine doses (250, 500, and 1,000 mg) using an active control dose of caffeine (200 mg) in 80 healthy participants. Caffeine had the expected effects on mood including feelings of alertness and cardiovascular parameters. Theobromine responses differed according to dose; it showed limited subjective effects at 250 mg and negative mood effects at higher doses. It also dose-dependently increased heart rate. In secondary analyses, we also examined individual differences in the drug's effects in relation to genes related to their target receptors, but few associations were detected. This study represents the highest dose of theobromine studied in humans. We conclude that theobromine at normal intake ranges may contribute to the positive effects of chocolate, but at higher intakes, effects become negative.
More about Parkinsonism after Taking Ecstasy
New England Journal of Medicine, 1999
To the Editor: Socié et al. (July 1 issue)1 reported on the long-term survival of patients who ha... more To the Editor: Socié et al. (July 1 issue)1 reported on the long-term survival of patients who have undergone alloge-neic bone marrow transplantation and the rate of death more than two years after transplantation. They provided in-formation on the characteristics and outcomes of ...
Preventing Problems in Ecstasy Users: Reduce Use to Reduce Harm
Journal of Psychoactive Drugs, 2002
Increasing use of 3,4-methylenedioxymethamphetamine (MDMA, "Ecstasy&... more Increasing use of 3,4-methylenedioxymethamphetamine (MDMA, "Ecstasy") has been accompanied by concern about acute and possible long-term toxicity. This article discusses acute serious toxicity, chronic toxicity, and common problems associated with Ecstasy use, as well as the implications of these areas for prevention programs targeted at current Ecstasy users. The low incidence of serious adverse events in users creates difficulties for attempts to develop harm reduction recommendations. Many hypothesized risk factors for serious adverse events cannot be confirmed or denied and may not be associated with dramatic elevations in risk. Research on chronic toxicity in users provides strong evidence of neurophysiological changes and suggestive evidence of possible neurocognitive changes. Because these worrisome changes are clinically subtle, users may not be influenced by concerns of neurotoxicity. In contrast, common Ecstasy-related complaints are relatively well documented and have identified risk factors, including factors relating to extent of Ecstasy use (such as "binges"). Common complaints include modest acute and subacute adverse effects,some lasting several days, and problems in life. The apparent willingness of users to modify drug use and other behaviors to decrease these common problems could be used by harm reduction or other prevention programs to encourage users to decrease the extent of Ecstasy use.
Journal of Pharmacology and Experimental Therapeutics, 2011
Qualitative urinalysis can verify abstinence of drug misuse but cannot detect changes in drug int... more Qualitative urinalysis can verify abstinence of drug misuse but cannot detect changes in drug intake. For drugs with slow elimination, such as methamphetamine (MA), a single episode of abuse can result in up to 5 days of positive urine drug screens. Thus, interventions that produce substantial decreases in drug use but do not achieve almost complete abstinence are classified as ineffective. Using nonpharmacologic doses of deuterium-labeled l-methamphetamine (l-MA-d 3 ) we have developed a simple, robust method that reliably estimates changes in MA intake. Twelve subjects were dosed with 5 mg of l-MA-d 3 daily and challenged with 15, 30, and 45 mg of nonlabeled d-MA (d-MA-d 0 ) after reaching plasma steady status of l-MA-d 3 . Urinary concentration ratios of d-MA-d 0 to l-MA-d 3 provided clear separation of the administered doses with as little as 15-mg dose increments. Administered doses could not be resolved using d-MA-d 0 concentrations alone. In conclusion, the urinary [d-MA-d 0 ]:[l-MA-d 3 ] provides a quantitative, continuous measure of illicit MA exposure.
Journal of Neurophysiology, 2008
A Randomized Placebo-Controlled Trial of Sustained-Release Amitriptyline in Primary Fibromyalgia
Journal Of Musculoskeletal Pain, 1996
... Wolfe F, Smythe HA, Yunus MB, Bennett RM, Bombardier C, Goldenberg DL, Tugwell P, Campbell SM... more ... Wolfe F, Smythe HA, Yunus MB, Bennett RM, Bombardier C, Goldenberg DL, Tugwell P, Campbell SM, Abeles M, Clark P, Farn AG, Farber SJ, Fiechtner JJ, Franklin CM, Gatter RA, Hamaty D, Lessard J, Lichtbroun AS, Masi AT, Mc-Cain GA, Reynolds WJ, Romano TJ, Rüssel IJ ...
Chemical Analysis of Ecstasy Pills
JAMA: The Journal of the American Medical Association, 2000
To the Editor: 3,4-Methylenedioxymethamphetamine (MDMA) has achieved notoriety as the drug &a... more To the Editor: 3,4-Methylenedioxymethamphetamine (MDMA) has achieved notoriety as the drug "ecstasy" and has been associated with dance events called "raves." Few reports of the content of ecstasy pills from the United States are available, 1 but European reports suggest that ...
Experimental and Clinical Psychopharmacology, 2013
Behavioral measures of impulsivity are widely used in substance abuse research, yet relatively li... more Behavioral measures of impulsivity are widely used in substance abuse research, yet relatively little attention has been devoted to establishing their psychometric properties, especially their reliability over repeated administration. The current study examined the test-retest reliability of a battery of standardized behavioral impulsivity tasks, including measures of impulsive choice (i.e., delay discounting, probability discounting, and the Balloon Analogue Risk Task), impulsive action (i.e., the stop signal task, the go/no-go task, and commission errors on the continuous performance task), and inattention (i.e., attention lapses on a simple reaction time task and omission errors on the continuous performance task). Healthy adults (n ϭ 128) performed the battery on two separate occasions. Reliability estimates for the individual tasks ranged from moderate to high, with Pearson correlations within the specific impulsivity domains as follows: impulsive choice (r range: .76 -.89, ps Ͻ .001); impulsive action (r range: .65-.73, ps Ͻ .001); and inattention (r range: .38 -.42, ps Ͻ .001). Additionally, the influence of day-to-day fluctuations in mood, as measured by the Profile of Mood States, was assessed in relation to variability in performance on each of the behavioral tasks. Change in performance on the delay discounting task was significantly associated with change in positive mood and arousal. No other behavioral measures were significantly associated with mood. In sum, the current analysis demonstrates that behavioral measures of impulsivity are reliable measures and thus can be confidently used to assess various facets of impulsivity as intermediate phenotypes for drug abuse.
Ketamine is associated with lower urinary tract signs and symptoms
Drug and Alcohol Dependence, 2013
Case reports and series indicate that ketamine, an anesthetic agent, causes lower urinary tract s... more Case reports and series indicate that ketamine, an anesthetic agent, causes lower urinary tract symptoms (LUTS). This study explored whether ketamine users were more likely to report LUTS compared to other substance users. Participants were recruited through an online survey on erowid.org, a drug information website. A notice posted on the website invited substance users to participate in a web-based survey on "drug use and health". The notice did not mention ketamine, or other aspects of the research questions, to avoid participation bias. The anonymous survey collected demographics, drug use history, and history of LUTS (urinary frequency, urgency, incontinence, hematuria, and dysuria). Of 18,802 participants, 18.7% and 5.8% reported ever (lifetime) and recent (past-6-month) use of ketamine, respectively. Prevalence of LUTS among ever, recent, and never users of ketamine were 28%, 30%, and 24% respectively. Multivariate analysis showed significant associations between recent ketamine use and urinary symptoms. For each additional day of ketamine use in the last 180 days, the odds of developing urinary frequency, urgency, dysuria, and hematuria increased by 1.6%, 1.4%, 1.7%, and 1.9% respectively. One excess case of urinary frequency was reported per 17 recent users of ketamine. Compared to non-users, recent ketamine users had increased odds of LUTS. This is the first large-scale community-based study assessing the association of non-medical ketamine use with LUTS. Associations between ketamine and urological symptoms should be confirmed through longitudinal studies.
Abnormal visual experiences in individuals with histories of hallucinogen use: A web-based questionnaire
Drug and Alcohol Dependence, 2011
Despite longstanding reports of prolonged or reoccurring perceptual changes in a subset of halluc... more Despite longstanding reports of prolonged or reoccurring perceptual changes in a subset of hallucinogen users, very little is known about Hallucinogen Persisting Perception Disorder and related visual abnormalities in hallucinogen users. We used an online questionnaire to document the symptoms and relationship to drug use of unusual visual phenomena in hallucinogen users. 16,192 individuals viewed the information sheet and 2679 were included in the study. Of these, 224 reported having unrelated diagnoses associated with unusual visual experiences and were excluded from main analyses. Most (60.6%) of the remaining 2455 participants reported having experienced drug-free visual experiences that resembled hallucinogen effects. Probability of experiencing constant or near-constant symptoms was predicted by greater past exposure to specific hallucinogens, including lysergic acid diethylamide (LSD). Although symptoms were common, few (104, or 4.2% of the sample) found them distressing or impairing enough to consider seeking treatment. Visual changes in hallucinogen users may be more common than previously suspected and are worthy of further study.
The effects of inhaled L-methamphetamine on athletic performance while riding a stationary bike: a randomised placebo-controlled trial
British Journal of Sports Medicine, 2009
L-methamphetamine (the non-abused isomer of methamphetamine) is banned in athletic competition be... more L-methamphetamine (the non-abused isomer of methamphetamine) is banned in athletic competition because it may improve athletic performance, but there are no studies assessing its effects on performance. In the United States L-methamphetamine is formulated in the non-prescription Vick's Vapor Inhaler (VVI) nasal decongestant. VVIs sold elsewhere (we used ones from the UK) contain similar inactive ingredients (menthol, camphor and Siberian pine oil) but no L-methamphetamine. This study tested the effects of inhaled L-methamphetamine delivered from a widely available non-prescription product on athletic performance. In a 2-session double-blind placebo-controlled study 12 participants (ages 14-17) were dosed with 4 (session 1) and 12 (session 2) inhalations from VVIs with (USA) or without (UK) L-methamphetamine and then performed two 20 minute rides on a stationary bike with rides separated by a 30 minute rest. The main outcome measure was miles travelled during each 20 minute ride. Secondary outcome measures included postride urine toxicology; heart rate and blood pressure before, 1, 5 and 10 minutes postride; energy, performance, endurance, and ability to breathe; and VVI preference. Data were analysed using Excel statistical macros. After approximately 16 microg L-methamphetamine distance travelled was 5.26 (SD 0.53) miles vs 5.30 (0.55) with placebo; p = 0.81. After approximately 48 microg L-methamphetamine distance travelled was 5.30 (0.51) vs 5.35 (0.43) with placebo; p = 0.85. The approximately 16 microg dose increased systolic blood pressure from 72.6 (4.3) to 79.6 (6.6) mm Hg (p = 0.03) at 5 minutes postride but there were no other differences in outcomes. Modest doses of inhaled L-methamphetamine probably do not improve athletic performance but do minimally raise diastolic blood pressure.
Annals of Internal Medicine, 2000
Background: The psychoactive stimulant 3,4-methylenedioxymethamphetamine (MDMA), also known as "e... more Background: The psychoactive stimulant 3,4-methylenedioxymethamphetamine (MDMA), also known as "ecstasy," is widely used in nonmedical settings. Little is known about its cardiovascular effects.
BACKGROUND: Psychedelic drugs facilitate profound changes in consciousness and have potential to ... more BACKGROUND: Psychedelic drugs facilitate profound changes in consciousness and have potential to provide insights into the nature of human mental processes and their relation to brain physiology. Yet published scientific literature reflects a very limited understanding of the effects of these drugs, especially for newer synthetic compounds. The number of clinical trials and range of drugs formally studied is dwarfed by the number of written descriptions of the many drugs taken by people. Analysis of these descriptions using machine-learning techniques can provide a framework for learning about these drug use experiences.
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Papers by Matthew Baggott