Euphoric Effects Research Articles

Critical Review of Alcohol, Alcoholism and the Withdrawal Symptoms I. Mechanisms of Addiction and Withdrawal Syndrome

Alcoholic beverages are socially accepted around the world, consumed mostly to socialize, celebrate, and relax. The pleasant effects of alcohol are attributed to (i) an increase in GABAergic (inhibitory signals), OPergic and 5HTergic (euphoric effects) neuronal activities and (ii) a decrease in DAergic ('want' signal or craving), Gluergic (excitatory signals), NEergic (stress signals) neuronal, and the HPA axis (stress hormones) activities. If alcohol drinking continues, the receptors are sensitized, resulting in development of tolerance when alcohol drinking must be increased to achieve desired effects. In genetically/Environmentally predisposed subjects, chronic alcohol drinking results in the development of addiction, characterized by a condition when alcohol caseation results in rapid onset of withdrawal symptoms including, but not limited to, alcohol craving and moderate to severe discomfort. Because pharmacotherapy alone or in combination with behavioral approaches is only modestly effective in treating alcoholism symptoms, there is an urgent need to development effective and safe therapies. At present, a lack of clear understanding of the mechanisms underlying addiction hinders possible development of new treatment strategies. Therefore, the aim of this article is to discuss the mechanisms underlying (i) the euphoric, relaxing and adverse effects of alcohol drinking and (ii) addiction and the withdrawal symptoms.

U-47700: The new emerging opioid drug

IntroductionThe trans-3;4-dichloro-N-(2-(dimethylamine) cyclohexyl) labelled as U-47700 has a high affinity with the selective receptor, considered to have 7.5 times the binding affinity of morphine; as a result, it is sold as a recreational drug because of its analgesic and euphoric effects. Several toxicity cases and some fatalities have been reported during 2016.ObjectivesTo describe the presence of trans-3;4-dichloro-N-(2-(dimethylamine) cyclohexyl) in samples delivered to Energy Control during 2016 in Barcelona.MethodsFrom January 2016 to October 2016, 4031 samples were delivered and only those samples containing trans-3;4-dichloro-N-(2-(dimethylamine) cyclohexyl) were studied, 6 of them were analysed as U-47700 (0.148%). Samples were analysed by energy control, a Spanish harm-reduction NGO that offers users the possibility of analysing the substances they intend to consume. Analysis was done by gas chromatography–mass spectrometry.ResultsFrom the 6 samples that were analysed as trans-3;4-dichloro-N-(2-(dimethylamine) cyclohexyl), the presentation of 4 of them was white powder and the rest were not described. The procedence of the samples was Canada (2), USA (1), Sweden (1), Holland (1) and the remaining sample was not described. All samples were received during 2016.ConclusionsThe use of trans-3;4-dichloro-N-(2-(dimethylamine)cyclohexyl) is progressively increasing in Barcelona. Its harmful effects are being reported in recent medical literature and consumption represents an emerging issue, gaining popularity among recreational opioid users. It is potentially lethal when mixed with depressants like alcohol or benzodiazepines and overdose risk is higher compared to other opioids. This drug is not being detected by routine in medical test.Disclosure of interestThe authors have not supplied their declaration of competing interest.

Effects of Short-Term Oxycodone Maintenance on Experimental Pain Responses in Physically Dependent Opioid Abusers.

To understand sensitivity to opioid analgesia in opioid-dependent individuals, this article describes experimental pain, subjective and physiological responses during stabilization and after 6weeks of oxycodone maintenance. Oxycodone produced euphoric effects and miosis with limited evidence of analgesia.

VENTRICULAR TACHYCARDIA TRIGGERED BY LOPERAMIDE AND FAMOTIDINE ABUSE

A 32-year-old male developed recurrent ventricular tachycardia after taking mega doses of loperamide and famotidine in order to experience an opiate-like euphoric effect. He was taking up to 200 mg of loperamide and multiple doses of famotidine each day. He developed palpitations and syncope. Electrocardiography demonstrated ventricular tachycardia and QT interval prolongation (corrected QT interval was 597 ms). He was diagnosed with loperamide-induced QT prolongation resulting in incessant ventricular tachycardia. Loperamide was discontinued, and he was treated with electrolyte replacement, supportive care, and monitoring. After 5 days, his electrocardiogram (ECG) normalized and he had no more ventricular tachycardia. A Naranjo assessment score of 8 was obtained, indicating a probable relationship between QT prolongation and his use of loperamide. Large doses of loperamide can cause QT interval prolongation and life-threatening arrhythmias. These effects may be accentuated when histamine-2 receptor blockers are also abused.

Zergatik egiten digu alkoholak kalte?

Gaur egun, alkohol-kontsumoa oso hedatua dago gure gizartean. Nahiz eta gizartearen aldetik oso onartua egon, iradoki izan da batetik efektu euforikoak eragiten dituela, eta bestetik asaldura fisiko zein psikiko kaltegarriak eragin diezazkiokeela organismoari. Alkoholaren zinetika nahiko aldakorra izan daiteke eta horrek nabarmen baldintzatzen ditu organismoan sortzen diren eragin akutuak. Bestalde, alkoholaren luzaroko kontsumoak ere efektu kaltegarriak ditu, esate baterako, menpekotasuna. Ondorioz, gizakiak alkoholdun edariak hartzeko behar handia sumatzen du. Horrekin lotuta, alkoholikoak tolerantzia garatuko du, eta gero eta alkohol kantitate handiagoak beharko ditu. Artikulu honetan, berrikusi egingo dira gorputzeko alkohol kontzentrazio handiagoak baldintzatzen dituzten prozesu zinetiko garrantzitsuenak, baita alkoholak eragindako efektu akutuak zein kronikoak ere.

Development and validation of the cannabis experiences questionnaire – Intoxication effects checklist (CEQ-I) short form

ObjectiveTo develop and validate a short form of the Cannabis Experiences Questionnaire - Intoxication Effects (CEQ-I), a 42-item scale which measures the euphoric and paranoid-dysphoric effects of cannabis intoxication. MethodExploratory and confirmatory factor analyses were conducted among 604 past-month cannabis users to develop the short form. The factor structure was replicated in a second sample of 146 past-month cannabis users. The concurrent validity of the scale was also examined. ResultsConsistent with previous research, two factors were identified (paranoid-dysphoric; euphoric), and were replicated with confirmatory factor analyses. The most parsimonious scale consisted of 13 items. Correlations of short-form subscales with corresponding original subscales were high. The paranoid-dysphoric subscale was also moderately positively correlated with measures of psychotic-like experiences (PLEs) and psychological distress. ConclusionsThe revised and validated CEQ-I short form can be used to explore the euphoric and paranoid-dysphoric effects of cannabis intoxication in young cannabis users, and whether these experiences increase their risk of developing cannabis use and psychotic disorders. The CEQ-I short form has the potential to aid in the identification of young cannabis users at risk of the paranoid-dysphoric effects of cannabis intoxication and may assist in the development of early intervention strategies targeting cannabis users with PLEs.

Adverse event detection using the FDA post-marketing drug safety surveillance system: Cardiotoxicity associated with loperamide abuse and misuse

ObjectiveThe purpose of this investigation was to identify and characterize post-marketing reports of cardiotoxicity, including torsades de pointes (TdP), associated with loperamide use. MethodsWe searched the U.S. Food and Drug Administration Adverse Event Reporting System (FAERS) database for post-marketing reports of serious cardiac adverse events associated with loperamide use from December 28, 1976 (U.S. drug approval date), through December 14, 2015. We also conducted a Pubmed and Google Scholar search to identify additional published reports of cardiotoxicity associated with loperamide in the medical literature through February 11, 2016. ResultsForty-eight cases of serious cardiac adverse events associated with loperamide use composed the case series. The most frequently reported cardiac adverse events were syncope (n = 24), cardiac arrest (n = 13), QT-interval prolongation (n = 13), ventricular tachycardia (n = 10), and TdP (n = 7). There were 10 cases that resulted in death. Of the 48 cases, the most commonly reported reasons for use can be characterized as drug abuse (n = 22) and diarrhea treatment (n = 17). More than one-half of the 48 cases were reported after 2010. Of the 22 drug abuse cases, the median daily dose was 250 mg (range 70 mg to 1600 mg) and events occurred as early as 6 hours after a dose and as long as 18 months after initiation of loperamide. Thirteen of the 22 cases reported using loperamide for euphoric or analgesic effects, and 9 reported use to prevent opioid withdrawal symptoms. ConclusionThe FAERS case reports provide evidence to suggest that high doses of loperamide are associated with TdP and other serious cardiac adverse events. The majority of cases in this series occurred in the setting of drug abuse for the purpose of preventing opioid withdrawal or to produce euphoric effects. It is important for both clinicians and patients to be aware of this potential risk, because prompt therapy and discontinuation of the offending agent are often essential to management and prevention of loperamide-induced cardiac arrhythmias.

Datura Stramonium Poisoning: Two Case Reports

Introduction: Datura stramonium is a wild plant, which grows in almost every region of Turkey and is found in the native flora. D. stramonium is used as a herbal medicine for asthma, bronchitis, eczema, and hemorrhoid treatment. Because of D. stramonium’s hallucinative and euphoric effects, it can be abused, particularly by drug addicts. Excessive oral intake may cause anticholinergic toxicity. In the case of a very high dose intake, it may result in coma. In this study, we have discussed two patients who presented to the emergency department of our hospital with anticholinergic findings and were diagnosed with D. stramonium intoxication.Case Report: Two patients presented to the emergency department of our hospital with signs and symptoms of anticholinergic poisoning. Two cases were also fell complaints with symptomatic treatment. Both the patients were admitted to the toxicology department and were followed-up for 2 days. The complaints regressed the next day, and the both the patients were discharged with complete recovery.Conclusion: Our study reporting the present cases shows that D. stramonium, which is used for therapeutic purposes, also causes severe intoxication. Therefore, wild plant poisoning should be considered for every patient presenting to the emergency department with unexplained anticholinergic symptoms and complaints

Effects of Tramadol Addiction on Brain of Adult Male Albino Rats and Role of lofexidine during Withdrawal Period: A Biochemical, Histopathological and Immunohistochemical Study

Background: Tramadol is a synthetic opioid analgesic commonly prescribed for moderate to severe pain, becoming abused more popular among teens in most countries. In addition to the euphoric and mood-enhancing effects sought by tramadol abusers, taking this drug for nonmedical purposes, abusing tramadol can lead to tolerance and dependence. Abusers who continue to take tramadol long enough and at high enough doses will eventually develop a physical dependence on the drug and experience unpleasant, or even dangerous, symptoms of withdrawal if they stop taking the medication. Objective: To study the biochemical, histopathological and immunohistochemical changes of repeated administration of tramadol on the brain cells of male albino rats and role of duration of addiction in the damaging effects produced, and to prove if there is a role for lofexidine in the treatment of tramadol addiction in withdrawal period and detect the changes after recovery period and withdrawal of tramadol .Materials and methods: 100 adult male albino rats were randomly divided into equal 5groups: Group I: (20 rats) Control group: including those given normal feeding. Group II: (20 rats) Tramadol treated group for one month. Group III: (20 rats) Tramadol treated group for 2 months. Group IV: (20 rats) Tramadol treated for one month then given lofexidine for another month during withdrawal. Group V: (20 rats) Tramadol treated for one month and left for another month for recovery. Animals were observed for any behavioral changes throughout the research and recorded. At the end of the experiment animals were scarified by cervical dislocation under inhalation anesthesia, autopsy was done and the brain specimens were obtained, prepared for biochemical study for dopamine level and others preserved for histopathological and immunohistochemical study with their specific procedures. Results: Repeated Tramadol administration resulted in rats behavioral changes( restlessness, irritability defensive aggressive reactions) and produced decreased dopamine levels and significant brain damage in the histopathological and immunohistochemical study that increased with increased period of intake (The maximum damage was recorded in group III with two months tramadol administration, varying degrees of recovery after stoppage of intake were noted in Group V and more improvement by Lofexidine treatment in Group IV). Conclusions: Repeated Tramadol administration causes degenerative changes on the rat brain which increased with increasing the period of this administration. Some improvement was detected after stoppage and more improvement with Lofexidine treatment in withdrawal period.

Neuropeptide systems and new treatments for nicotine addiction.

The mildly euphoric and cognitive enhancing effects of nicotine play a role in the initiation of smoking, while dysphoria and anxiety associated with smoking cessation contribute to relapse. After the acute withdrawal phase, smoking cues, a few cigarettes (i.e., lapse), and stressors can cause relapse. Human and animal studies have shown that neuropeptides play a critical role in nicotine addiction. The goal of this paper is to describe the role of neuropeptide systems in the initiation of nicotine intake, nicotine withdrawal, and the reinstatement of extinguished nicotine seeking. The reviewed studies indicate that several drugs that target neuropeptide systems diminish the rewarding effects of nicotine by preventing the activation of dopaminergic systems. Other peptide-based drugs diminish the hyperactivity of brain stress systems and diminish withdrawal-associated symptom severity. Blockade of hypocretin-1 and nociceptin receptors and stimulation of galanin and neurotensin receptors diminishes the rewarding effects of nicotine. Both corticotropin-releasing factor type 1 and kappa-opioid receptor antagonists diminish dysphoria and anxiety-like behavior associated with nicotine withdrawal and inhibit stress-induced reinstatement of nicotine seeking. Furthermore, blockade of vasopressin 1b receptors diminishes dysphoria during nicotine withdrawal, and melanocortin 4 receptor blockade prevents stress-induced reinstatement of nicotine seeking. The role of neuropeptide systems in nicotine-primed and cue-induced reinstatement is largely unexplored, but there is evidence for a role of hypocretin-1 receptors in cue-induced reinstatement of nicotine seeking. Drugs that target neuropeptide systems might decrease the euphoric effects of smoking and improve relapse rates by diminishing withdrawal symptoms and improving stress resilience.

Notes from the Field: Cardiac Dysrhythmias After Loperamide Abuse - New York, 2008-2016.

Loperamide is an over-the-counter antidiarrheal with opioid-receptor agonist properties. Recommended over-the-counter doses (range=2-8 mg daily) do not produce opioid effects in the central nervous system because of poor oral bioavailability and P-glycoprotein efflux* of the medication (1); recent reports suggest that large doses (50-300 mg) of loperamide produce euphoria, central nervous system depression, and cardiotoxicity (2-4). Abuse of loperamide for its euphoric effect or for self-treatment of opioid withdrawal is increasing (5). Cases of loperamide abuse reported to the Upstate New York Poison Center and New York City Poison Control Center were analyzed for demographic, exposure, clinical, and laboratory characteristics. Cases of intentional loperamide abuse reported to the National Poison Database System (NPDS) also were analyzed for demographic, dose, formulation, and outcome information.

Epidemiologic Trends in Loperamide Abuse and Misuse

Loperamide abuse has been increasing in the United States as a potential alternative to manage opioid withdrawal symptoms or to achieve euphoric effects of opioid use. In June 2016, the Food and Drug Administration warned health care providers and the general public about potential serious adverse outcomes, including cardiac dysrhythmias and death. The purpose of this study is to determine recent trends in intentional loperamide abuse and misuse, reported clinical effects and management, and medical outcomes as reported to poison centers across the United States. Loperamide exposures reported to the National Poison Data System indicating intentional misuse, abuse, and suspected suicide between January 1, 2010, and December 31, 2015, were assessed. Demographic and temporal trends, as well as reported clinical effects, medical management, and health outcomes, were analyzed. There was a 91% increase in reported exposures from 2010 to 2015, of which half were single-agent loperamide use only. Loperamide exposures reported to the National Poison Data System increased at approximately 38 cases per year (95% confidence interval [CI] 32.5 to 42.9; P<0.0001). Fifteen deaths were reported during this time frame, of which 8 involved single-agent loperamide abuse. Loperamide abuse and misuse are projected to increase in the absence of any methods to reduce exposure or curb abuse. Health care providers should consider the potential for loperamide toxicity when managing patients with opioidlike toxicity.

10.2 Effect of an Opioid Receptor Antagonist on Stimulant Treatment of Adults With Attention-Deficit/Hyperactivity Disorder

Preclinical studies have shown that methylphenidate (MPH) activates mu opioid receptors, which are linked to euphoria. It is possible that mu opioid antagonists, such as naltrexone, may attenuate the euphoric effects of stimulants, thereby minimizing their abuse potential. The main aim of this study was to assess whether the combination of naltrexone with MPH is safe and effective and whether it preserves the clinical benefits of stimulants. We hypothesized that the coadministration of naltrexone would not affect the therapeutic potency of stimulants in the treatment of subjects with ADHD.

Glue sniffing

Inhalant abuse refers to the inhalation of volatile substances for their euphoric effects. Glues and adhesives have been abused inhalants for decades and so the term "glue sniffing" attached to the habit. These days many substances used are not adhesives and the most accurate title of "solvent abuse" has been given to this widespread and dangerous habit. The various methods of inhalational abuse include huffing, bagging, dusting, glading, and sniffing. We report one such case of a 22-year-old male who was found in an unresponsive state at his residence with a plastic cover around his head and empty tubes of "Fevibond" glue beside him. He died on the way to hospital. At autopsy, conjunctival and visceral congestion were found with pulmonary edema and petechiae over visceral pericardium. The viscera were analyzed, and the presence of toluene in his liver and blood was reported.

Epidemiology of Use of a Traditional Spirit “Sodabi” in the General Population of Togo

The purpose of this paper is to evaluate the profile of sodabi consumption in the Togolese population. This transverse descriptive study was conducted over a nine month period from June 9, 2013 to March 9, 2014, throughout the five regions of Togo. Findings demonstrated a clear profile of 2388 sodabi drinkers. 1672 (70.02%) men and 716 (29.98%) women. Prevalence was 62.45% in the population studied. Mean age was 35.3 years. Almost all subjects interrogated (98.48%) were togolese nationals. The study included the following ethnic and regional groups, the Kabyè-Tem ethnic group (43.59%) and the Paragourma-Akan groups (23.50%) were the most represented among the subjects interrogated. More than a third (25.67%) of subjects interviewed was unemployed with a higher unemployment rate in the Maritime region and Lomé Commune (37.16%). Most of the people interrogated (49.66%) were living as couples (married or cohabiting). 4.06% of subjects drank sodabi only. 51.40% of drinkers abused sodabi (40.59% men against 10.81% women). The prevalence of noxious alcohol use was high (12.35%) among unemployed participants. 25.51% of drinkers visited drinking establishments once a week and 22.10% almost every day. The euphoric effect of alcohol (45.23%) and friendly atmosphere (19.39%) of the drinking establishment were the main reasons for attendance (64.62%). Of the damage caused by the abuse of sodabi, 39.26% of subjects showed somatic or neurological complications and 60.74% psychological and psychiatric complications. Updating these data seems necessary, because combating excessive drinking is one of the main objectives of current togolese public health policy.

NATURAL PSYCHODYSLEPTIC COMPOUNDS: SOURCES AND PHARMACOLOGY

ABSTRACTCompounds in some plants have remarkable effects on the central nervous system. Plants containing those compounds are mind altering orpsychoactive in nature. These are consumed in the form of simple or complex preparations to affect the mind or alter the state of consciousness.Psychoactivity may include sedative, stimulant, euphoric, deliriant, and hallucinogenic effects. Several hundred psychoactive plants are known.Some important examples of psychoactive plants include Datura, Salvia, and Cannabis. Psychoactive plants have been used ritually, medicinally, andrecreationally for thousands of years. Hence, the sociocultural and economic significance of psychoactive plants is enormous.Keywords: Cannabis, Datura, Psychoactive plants, Euphoria, Hallucinogen.

Non-Prescribed Buprenorphine in New York City: Motivations for Use, Practices of Diversion, and Experiences of Stigma

Non-medical use of opioid analgesics (OAs) has increased in the United States over the past decade. Concurrently, access to opioid agonist therapies (OATs) such as buprenorphine has expanded. However, there has been little in-depth qualitative exploration into circumstances surrounding buprenorphine diversion and non-prescribed use. This study reports on qualitative data from in-depth interviews conducted with persons in New York City reporting non-medical OA use in the past 12 months. Participants (n=42) were aged between 18 and 49 years. The majority were male (n=29) and non-Hispanic White (n=35). All participants self-reported physical opioid dependence. Motivations for non-prescribed buprenorphine use included the abatement of withdrawal symptoms or a self-initiated detoxification or treatment plan. Few participants reported buprenorphine use for euphoric effect, and no participants reported using buprenorphine as a primary drug. Buprenorphine diversion primarily occurred as a means of supporting ongoing illicit drug use, and no participants reported selling buprenorphine as a primary source of income. Participants reported misinformation around some key areas of buprenorphine induction and use, as well as stigma within peer networks and from drug treatment providers. As access to buprenorphine treatment continues to expand in the United States, enhancing patient education is a critical step toward minimizing diversion and incidental harms from non-prescribed use.

Stimulants for the Control of Hedonic Appetite.

The focus of this paper is treatment of obesity in relation to the management of hedonic appetite. Obesity is a complex condition which may be potentiated by excessive reward seeking in combination with executive functioning deficits that impair cognitive control of behavior. Stimulant medications address both reward deficiency and enhance motivation, as well as suppressing appetite. They have long been recognized to be effective for treating obesity. However, stimulants can be abused for their euphoric effect. They induce euphoria via the same neural pathway that underlies their therapeutic effect in obesity. For this reason they have generally not been endorsed for use in obesity. Among the stimulants, only phentermine (either alone or in combination with topiramate) and bupropion (which has stimulant-like properties and is used in combination with naltrexone), are approved by the United States Food and Drug Administration (FDA) for obesity, although dexamphetamine and methylpenidate are approved and widely used for treating attention deficit hyperactivity disorder (ADHD) in adults and children. Experience gained over many years in the treatment of ADHD demonstrates that with careful dose titration, stimulants can be used safely. In obesity, improvement in mood and executive functioning could assist with the lifestyle changes necessary for weight control, acting synergistically with appetite suppression. The obesity crisis has reached the stage that strong consideration should be given to adequate utilization of this effective and inexpensive class of drug.

Not your regular high: cardiac dysrhythmias caused by loperamide

Objective: Loperamide, a non-prescription anti-diarrheal agent, is a peripheral mu-opioid receptor agonist that is excluded from the blood-brain barrier by p-glycoprotein at therapeutic doses. Overdoses of loperamide penetrate the central nervous system (CNS), leading to abuse. We report cardiac conduction abnormalities and dysrhythmias after ingestion of a recreational supra-therapeutic dose of loperamide confirmed with an elevated blood loperamide concentration. Case details: A 48-year-old woman with a history of alcohol and benzodiazepine abuse presented to the emergency department (ED) with somnolence, weakness and slurred speech. She was taking 20 to 40 tablets of 2 mg loperamide 1–2 times/day for weeks along with clonazepam and whiskey. Vital signs were: blood pressure (BP), 124/90 mmHg; heart rate (HR), 88/min; respiratory rate(RR), 20/min; T, 36.9 °C; O2 saturation 100% on room air (RA). Glucose was 6.4 mmol/L. Electrocardiogram (ECG) had a ventricular rate of 58/min, QRS 164 ms, QT 582 ms with no discernable p-waves. Lactate was 3.5 mmol/L and potassium was 6.2 mEq/L. Labs were notable for an anion gap of 20 mEq/L, ethanol of 3.9 mmol/L, creatinine of 2.3 mg/dL and loperamide concentration of 210 ng/mL (average therapeutic plasma concentration 1.2 ng/mL). She became hypotensive, but responded to fluids. Following treatment for hyperkalemia with calcium, insulin, dextrose, and hypertonic sodium bicarbonate a repeat ECG had a ventricular rate of 66/min, QRS 156 ms, and QT 576 ms. Magnesium was given and pacer pads were placed. During the infusion of magnesium, her BP fell to 92/58 mmHg with a HR of 54/min, RR 14/min, O2 saturation of 97% on RA so the infusion was stopped. The ECG after the magnesium infusion had a ventricular rate of 51/min, QRS of 134 ms, and QT 614 ms. In the ICU she had multiple runs of non-sustained ventricular tachycardia that did not require therapy. Over the next 48 h she improved and was transferred to a floor bed. On day four of hospitalization the patient left against medical advice. At that time, her ECG showed sinus tachycardia with a heart rate 114/min, QRS 82 ms, QT 334 ms. Discussion: Loperamide produces both QRS and QT prolongation at supra-therapeutic dosing. A blood loperamide concentration of 210 ng/mL is among the highest concentrations reported. Supra-therapeutic dosing of loperamide is promoted on multiple drug-use websites and online forums as a treatment for opioid withdrawal, as well as for euphoric effects. With the current epidemic of prescription opioid abuse, toxicity related to loperamide, an opioid agonist that is readily available without a prescription is occurring more frequently. It is important for clinicians to be aware of the potentially life-threatening toxicity related to loperamide abuse in order to provide proper diagnosis, management and patient education.

Individual differences in timing of peak positive subjective responses to d-amphetamine: Relationship to pharmacokinetics and physiology.

Rate of delivery of psychostimulants has been associated with their positive euphoric effects and potential addiction liability. However, information on individual differences in onset of d-amphetamine's effects remains scarce. We examined individual differences in the time to peak subjective and physiological effects and the pharmacokinetics/pharmacodynamics of oral d-amphetamine. We considered two independent studies that used different dosing regimens where subjects completed the drug effects questionnaire at multiple time points post d-amphetamine. Based on the observation of distinct individual differences in time course of drug effects questionnaire "feel", "high", and "like" ratings (DEQH+L+F) in Study 1, subjects in both studies were categorized as early peak responders (peak within 60 minutes), late peak responders (peak > 60 minutes) or nonresponders; 20-25% of participants were categorized as early peak responders, 50-55% as late peak responders and 20-30% as nonresponders. Physiological (both studies) and plasma d-amphetamine (Study 1) were compared among these groups. Early peak responders exhibited an earlier rise in plasma d-amphetamine levels and more sustained elevation in heart rate compared to late peak responders. The present data illustrate the presence of significant individual differences in the temporal pattern of responses to oral d-amphetamine, which may contribute to heightened abuse potential.