Profile Of Subjective Effects Research Articles

The acute effects of classic psychedelics on memory in humans.

Memory plays a central role in the psychedelic experience. The spontaneous recall and immersive reliving of autobiographical memories has frequently been noted by researchers and clinicians as a salient phenomenon in the profile of subjective effects of classic psychedelic drugs such as psilocybin, LSD, and ayahuasca. The ability for psychedelics to provoke vivid memories has been considered important to their clinical efficacy. This review aims to examine and aggregate the findings from experimental, observational, and qualitative studies on the acute modulation of memory by classic psychedelics in humans. A literature search was conducted using PubMed and PsycInfo as well as manual review of references from eligible studies. Publications reporting quantitative and/or qualitative findings were included; animal studies and case reports were excluded. Classic psychedelics produce dose-dependently increasing impairments in memory task performance, such that low doses produce no impairment and higher doses produce increasing levels of impairment. This pattern has been observed in tasks assessing spatial and verbal working memory, semantic memory, and non-autobiographical episodic memory. Such impairments may be less pronounced among experienced psychedelic users. Classic psychedelics also increase the vividness of autobiographical memories and frequently stimulate the recall and/or re-experiencing of autobiographical memories, often memories that are affectively intense (positively or negatively valenced) and that had been avoided and/or forgotten prior to the experience. Classic psychedelics dose-dependently impair memory task performance but may enhance autobiographical memory. These findings are relevant to the understanding of psychological mechanisms of action of psychedelic-assisted psychotherapy.

Abuse liability of electronic cigarettes in men who are experienced electronic cigarette users.

Most electronic cigarettes (e-cigs) aerosolize a nicotine-containing liquid that users inhale. Few experimental studies have examined e-cig abuse liability (the extent to which use of these products may lead to persistent and/or problematic use). In this study, 24 experienced male e-cig users completed 4 sessions that differed byproduct used: own e-cig (OWN), an eGo e-cig filled with participants' own brand/flavor liquid in 0 mg/mL nicotine (e-cig0), an eGo e-cig filled with the highest nicotine concentration available in participants' own brand/flavor (e-cighighest), and a U.S. Food and Drug Administration-approved nicotine inhaler (IN). Outcome measures included crossover point on the multiple-choice procedure, plasma nicotine delivery, and subjective effect profile. After 10 puffs, a significantly higher mean crossover point was observed for OWN at $1.35 (SD = 0.90) compared to e-cighighest at $0.88 (SD = 0.89), e-cig0 at $0.83 (SD = 0.79), and IN at $0.72 (SD = 0.84). Significant increases in mean plasma nicotine concentration were observed for OWN at 7.94 ng/mL (SD = 6.19) and e-cighighest at 7.51 ng/mL (SD = 5.39). Significant reductions in abstinence symptom suppression and higher ratings of satisfaction were observed for OWN and e-cighighest, with significantly less suppression and lower ratings of satisfaction for e-cig0 and IN. These findings suggest that human laboratory methods can be used to assess e-cig abuse liability and that nicotine-containing e-cigs have greater abuse liability than nicotine-free e-cigs and the IN. Potential regulations intended to limit e-cig abuse liability should be tested using these or similar procedures. (PsycInfo Database Record (c) 2020 APA, all rights reserved).

Subjective effects of combustible, vaporized, and edible cannabis: Results from a survey of adolescent cannabis users

BackgroundData from controlled laboratory experiments in adults indicate that the subjective effects of cannabis vary by administration method (e.g., combustible, vaporized). Whether the subjective effects of cannabis experienced in the natural ecology and among adolescents differ by cannabis administration method is unknown. In this observational study, adolescents’ retrospective reports of subjective effects after combustible, edible, and vaporized cannabis use were examined. MethodsStudents from ten public schools in Los Angeles, CA, USA (M[SD] age = 16.1 [.43] years) who reported past 6-month use of combustible, edible, or vaporized cannabis (N = 584) were surveyed on subjective effects experienced after use (yes/no). They were provided with a 12 item self-report checklist of six positive (e.g., relaxed, energetic) and six negative (e.g., drowsy, lazy) subjective effects. For each method of administration, affirmative responses were summed in positive (range: 0–6) and negative (range: 0–6) effect composite scores. ResultsGeneralized estimating equations adjusted for demographics and recent cannabis use revealed a graded pattern of differences in positive subjective effects across products, with highest scores for combustible (M[SD] = 3.98[1.76]), followed by edible (M[SD] = 3.58 [2.04]) and vaporized (M[SD] = 3.11 [2.21]) cannabis (all pairwise cross-product contrasts p < .01). Mean negative effect score was highest for edible (M[SD] = 2.27 [1.95]), followed by combustible (M[SD] = 1.94 [1.66]), and vaporized (M[SD] = 1.34 [1.73]) cannabis, respectively (all pairwise contrasts p < .02). ConclusionAdolescents’ reports of subjective effects varied across cannabis administration methods. Combustible cannabis’ more desirable subjective effects profile might be indicative of higher abuse liability.

Gender differences in associations between neurocognitive impairment and cocaine use among high-risk cocaine-dependent methadone-maintained patients

reuptake, the potential for misuse and abuse should be considered. This exploratory study assessed CTN’s abuse potential in recreational stimulant users. Methods: In this double-blind, randomized 5-way crossover study, 36 recreational stimulant users received single oral doses of CTN (400 and 800mg), damphetamine (d-AMP 40mg), lisdexamfetamine (LDX 150mg) and placebo. Eligible subjects passed a qualification session to ensure they could discriminate and like the effects of dAMP. In the treatment phase, subjective effects (visual analog scales [VAS], Addiction Research Center Inventory [ARCI] scales) and safety measures were assessed up to 24h after each dose. Results:Maximum Drug Liking VAS (DL Emax) was significantly higher for d-AMP and LDX vs. placebo (p<0.05), confirming study validity. DL Emax for CTNwas higher than placebo and numerically, but not statistically lower than dAMP and LDX. MinimumDL (Emin) for CTN was significantly lower compared to placebo, dAMP and LDX, indicating significant disliking. Bad Effects and Nausea VAS scores revealed distinct aversive effects of CTN compared with dAMP, LDX and placebo. CTN had significantly lower Emax scores on ARCI Amphetamine and ARCI Benzedrine Group scales compared with d-AMP and LDX. CTN was associated with a higher incidence of nausea (e.g., 56.3% at 800mg) and emesis (59.4%) vs. d-AMP, LDX and placebo (0–3%). Conclusions: These exploratory results indicate that CTN’s subjective effects profile is distinct from that of dAMP and LDX, and suggest a lower abuse potential compared with these typical stimulants. Financial support: Neurovance, Inc.

Emotional traits predict individual differences in amphetamine-induced positive mood in healthy volunteers.

Previous research on emotional correlates of individual differences in subjective responses to D-amphetamine has focused on relatively broad personality traits. Yet, emotional functioning is best characterized by several narrow subcomponents, each of which may contribute uniquely to amphetamine response. Here, we examine several specific subdomains of emotional functioning in relation to acute amphetamine response. At a baseline session, healthy stimulant-naive volunteers (N = 97) completed measures of several subdomains of baseline trait emotional functioning and then completed two counterbalanced experimental sessions during which they received a single oral dose of 20mg D-amphetamine or placebo. Acute subjective drug response measures were completed at repeated intervals before and after drug administration. Data from subjective measures that were significantly modulated by amphetamine were reduced using principal component analysis (amphetamine or placebo) into three higher-order factors of "positive mood," "arousal," and "drug high." Amphetamine did not significantly alter any "negative" subjective states. Separate multiple regression analyses were conducted regressing these three drug factors on baseline trait emotional functioning scales. The combined set of trait emotional functioning indicators accounted for approximately 22% of the variance in acute amphetamine-induced positive mood changes. Greater anticipatory pleasure and greater anxious distress each uniquely predicted greater amphetamine-induced positive mood. Trait emotional functioning did not significantly predict amphetamine-induced changes in arousal or drug high. Emotional traits appear to moderate drug-induced positive mood but not other dimensions of amphetamine effects. Different facets of emotional functioning may differentially modulate amphetamine's subjective effect profile.

4-Fluoroamphetamine in the Netherlands: more than a one-night stand.

To investigate the temporal pattern of appearance of a new psychoactive substance (4-fluoroamphetamine) on the Dutch drug market, as well as its patterns of use and effects. Data from the Drug Information and Monitoring System (DIMS) was used to investigate the emergence of 4-fluoroamphetamine on the Dutch drug market. An on-line questionnaire was used to study its patterns of use and effects. Dutch drug-related websites and social media. A convenience sample of 249 life-time 4-fluoroamphetamine users was recruited through the internet. Samples containing 4-fluoroamphetamine were extracted from the DIMS database for further investigation. Patterns of use, settings of use and the subjective effects of 4-fluoroamphetamine, amphetamine and 3,4-methylenedioxymethamphetamine (MDMA) were investigated with the on-line questionnaire. 4-Fluoroamphetamine was first encountered on the Dutch drug market, sold mainly as amphetamine or ecstasy (MDMA), between 2007 and 2009. These misrepresented drug samples declined when the MDMA and amphetamine markets recovered after a period of shortage, whereas purposefully bought 4-fluoroamphetamine samples showed an increase. Survey results showed that 4-fluoroamphetamine is used predominantly [77.1%, 95% confidence interval (CI) = 72.0-82.3] for its specific effects, rather than its legal status (17.7%, 95% CI = 10.7-22.1). The subjective effects of 4-fluoroamphetamine were compared with those of amphetamine and MDMA. Subjective effect scores of 4-fluoroamphetamine ranged between those of amphetamine and MDMA. The stimulant 4-fluoroamphetamine is increasingly popular in the Netherlands, which might be due to its subjective effects profile, which lies intermediate between amphetamine and MDMA.

Relationship between oral D-amphetamine self-administration and ratings of subjective effects: do subjective-effects ratings correspond with a progressive-ratio measure of drug-taking behavior?

The abuse potential of drugs has traditionally been determined in humans using subjective ratings of drug effects. However, drug self-administration procedures also provide valuable information about the reinforcing effects of drugs that may contribute to their potential for abuse. Although ratings of subjective effects and drug self-administration data are generally concordant, some divergent findings have been reported. Therefore, the aim of the present analysis was to directly investigate the relationship between the subjective-effects profile and self-administration of oral D-amphetamine in healthy volunteers with a history of stimulant use or abuse, using Pearson's correlational analyses. The results indicated that positive subjective and reinforcing effects significantly increased as a function of D-amphetamine dose. Further, significant, but modest, correlations were observed between ratings of six of 17 total items (Any Effect, High, Like Drug, Good Effects, Willing to Pay For, and Willing to Take Again) and D-amphetamine self-administration under a progressive-ratio schedule of reinforcement. The current findings suggest that, at least under the current set of conditions with oral D-amphetamine, subjective-effects measures and drug self-administration data likely provide different but complimentary information about abuse potential. The most informative findings will thus be obtained from studies that use ratings of subjective effects and drug self-administration methods.

Responses to alcohol and cigarette use during ecologically assessed drinking episodes

Tobacco and alcohol are frequently used together, and this may be partly explained by a distinct profile of subjective effects associated with co-administration. Ecological momentary assessment studies have examined effects of naturally occurring co-use, but, to date, have not assessed differing effects as alcohol levels rise and fall. The objective of the study was to describe subjective states and appraisals of cigarette and alcohol effects reported during the entirety of real-world drinking episodes. Currently-smoking frequent drinkers (N = 255) carried electronic diaries for 21 days. Analyses focused on reports made during 2,046 drinking episodes. Signaled prompts intensively oversampled moments in the hours following consumption of the first drink in an episode. Multilevel regression analyses were used to predict ratings of buzz, dizziness, excitement, and sluggishness as a function of person-level and contextual covariates, estimated blood alcohol concentration (eBAC) level, ascending vs. descending eBAC, smoking, and their interactions. Appraisals of cigarette and alcohol effects were also examined within this framework. Buzz, excitement, and pleasure from alcohol and cigarettes were prominent features of real-world drinking episodes. Smoking was associated with enhanced buzz and excitement when eBAC was high and descending. Smoking slightly accentuated the relation between eBAC and ratings of drinking pleasure among women, but this relation was somewhat weakened by smoking among men. Smoking during drinking episodes may be partly explained by a persistence of stimulant alcohol effects beyond the blood alcohol concentration peak. Acute effects of nicotine and tobacco use on the descending limb deserve further scrutiny in experimental alcohol challenge research.

4-Bromo-2,5-dimethoxyphenethylamine (2C-B): presence in the recreational drug market in Spain, pattern of use and subjective effects

4-Bromo-2,5-dimethoxyphenethylamine (2C-B) is a psychoactive analogue of mescaline that is becoming increasingly popular as a rave and club drug. We investigated its presence in the illicit drug market in Spain, its pattern of use and profile of subjective effects. Drug material was analysed for 2C-B and information on pattern of use and subjective effects was obtained from recreational users. Scores were statistically compared with previously collected data on psychostimulants (d-amphetamine), entactogens (MDMA) and psychedelics (ayahuasca and Salvia divinorum). The percentage of samples containing 2C-B doubled between 2006 and 2009, evolved from powder to tablet form and showed low falsification rates. Respondents reported taking 2C-B orally in doses of about 20 mg. Subjective effects involved perceptual modifications analogous to those observed after ayahuasca and salvia but absent after amphetamine and MDMA. Pleasure and sociability effects did not differ from those after MDMA and incapacitation was lower than for the psychedelics used as comparators. In conclusion, we found 2C-B is consistently present in the illicit drug market in Spain. While it elicits perceptual modifications that are analogous to other psychedelics, the lower impairment and higher pleasurable effects make it comparable with entactogens.

Multiple dopamine receptors mediate the discriminative stimulus effects of dihydrexidine in rats

The dopamine D(1) receptor agonist dihydrexidine (DHX) [(±)-trans-10,11-dihydroxy-5,6,6a,7,8,12b-hexahydrobenzo[a] phenanthridine hydrochloride] has shown efficacy in animal models of Parkinson's disease and improved cerebral blood flow and working memory of schizophrenic patients. Although the discriminative stimulus effects of DHX, an in-vivo predictor of human subjective effect profile, have only been characterized with respect to activity at D(1) receptors, DHX also has significant affinity for D(2) receptors. This study was designed to characterize the role of D(1) and D(2)/D(3) receptors in mediating the discriminative stimulus effects of DHX. Rats were trained to discriminate DHX [3 mg/kg, intraperitoneally (i.p.)] from the vehicle. The selective dopamine D(1) receptor partial agonist SKF 38393 was fully substituted for DHX. The D(1) receptor antagonist SCH 23390 (0.1 mg/kg, s.c.) and the D(3)-selective antagonist U99194 (10 mg/kg, i.p.) significantly attenuated the discriminative stimulus effects of the training dose of DHX by 80 and 60%, respectively, suggesting that both D(1) and D(3) receptors mediate the discriminative stimulus effects of DHX. In contrast, raclopride (1 mg/kg, i.p.) did not significantly alter the discriminative stimulus effects of DHX, indicating a lack of D(2)-mediated effects. The D(2)/D(3) receptor preferring agonists, quinpirole and (+)-PD 128907 were fully substituted, whereas (+)-7-OH-DPAT was partially substituted for DHX. The DHX bound to D(2) receptors with a Ki of 4.3+0.7 nmol/l was compared with 33.7+4.6 nmol/l at D(3) receptors. Determinations of activity at second messenger systems revealed that DHX functioned as a full agonist at D(3) receptors and a partial agonist at D(2) receptors in vitro. These activities at D(2)/D(3) receptors have shown effects in some preclinical models and clinical disease states. Therefore, the prominent in-vivo agonist activity of DHX at both D(1) receptors and D(2)/D(3) receptors should be considered while making predictions of effects in humans.

Mephedrone: use, subjective effects and health risks

To assess the patterns of use, subjective effect profile and dependence liability of mephedrone, supported by corroborative urine toxicology. Cross-sectional structured telephone interview. UK-based drug users associated with the dance music scene. A total of 100 mephedrone users, recruited through their involvement with the dance music scene. Assessment of pattern of use, acute and after effects, DSM dependence criteria and gas chromatography-mass spectrometry urinalysis. Mephedrone consumption results in typical stimulant-related subjective effects: euphoria, increased concentration, talkativeness, urge to move, empathy, jaw clenching, reduced appetite and insomnia. Thirty per cent of the sample potentially met criteria for DSM-IV dependence and there was evidence of a strong compulsion to use the drug (47% had used the drug for 2 or more consecutive days). Self-reported recent consumption of mephedrone was confirmed by toxicological analysis in all of the 14 participants who submitted a urine sample. Mephedrone has a high abuse and health risk liability, with increased tolerance, impaired control and a compulsion to use, the predominant reported dependence symptoms.

Human psychopharmacology and dose-effects of salvinorin A, a kappa opioid agonist hallucinogen present in the plant Salvia divinorum

Salvinorin A is a potent, selective nonnitrogenous kappa opioid agonist and the known psychoactive constituent of Salvia divinorum, a member of the mint family that has been used for centuries by Mazatec shamans of Mexico for divination and spiritual healing. S. divinorum has over the last several years gained increased popularity as a recreational drug. This is a double-blind, placebo controlled study of salvinorin A in 4 psychologically and physically healthy hallucinogen-using adults. Across sessions, participants inhaled 16 ascending doses of salvinorin A and 4 intermixed placebo doses under comfortable and supportive conditions. Doses ranged from 0.375μg/kg to 21μg/kg. Subject-rated drug strength was assessed every 2min for 60min after inhalation. Orderly time- and dose-related effects were observed. Drug strength ratings peaked at 2min (first time point) and definite subjective effects were no longer present at approximately 20min after inhalation. Dose-related increases were observed on questionnaire measures of mystical-type experience (Mysticism Scale) and subjective effects associated with classic serotonergic (5-HT2A) hallucinogens (Hallucinogen Rating Scale). Salvinorin A did not significantly increase heart rate or blood pressure. Participant narratives indicated intense experiences characterized by disruptions in vestibular and interoceptive signals (e.g., change in spatial orientation, pressure on the body) and unusual and sometimes recurring themes across sessions such as revisiting childhood memories, cartoon-like imagery, and contact with entities. Under these prepared and supportive conditions, salvinorin A occasioned a unique profile of subjective effects having similarities to classic hallucinogens, including mystical-type effects.

Atomoxetine: a review of its use in adults with attention deficit hyperactivity disorder.

Atomoxetine (Strattera) is a selective norepinephrine reuptake inhibitor and nonstimulant that has shown greater efficacy than placebo in attention deficit hyperactivity disorder (ADHD) in adults. In two large, well controlled, 10-week trials in adults with ADHD, improvements in ADHD symptoms, as assessed by investigator- and patient-rated scores, were greater with oral atomoxetine (60, 90 or 120 mg/day) than with placebo. Mean reductions in the total ADHD symptom score on the investigator-rated Conners' Adult ADHD Rating Scale (CAARS) in atomoxetine versus placebo recipients were 28.3% versus 18.1% and 30.1% versus 19.6%, respectively. Mean reductions in the scores on the Clinician Global Impression of Severity Scale, patient-rated CAARS and Wender-Reimherr Adult Attention Deficit Disorder Scale were also significantly greater with atomoxetine than with placebo. Continued efficacy was demonstrated in a noncomparative, 34-week extension phase. Atomoxetine was generally well tolerated in clinical trials; withdrawal rates due to adverse events in atomoxetine-treated versus placebo-treated patients participating in the two major trials were 7.8% versus 4.3% and 9.3% versus 2.4% (p<0.05 for the latter trial). Adverse events reported significantly more frequently with atomoxetine than placebo included dry mouth, insomnia, nausea, decreased appetite, constipation, dizziness, sweating, dysuria, sexual problems and palpitations. Modest increases in heart rate and blood pressure were well tolerated and gradually decreased on cessation of treatment. Atomoxetine was not associated with QT interval prolongation. Atomoxetine can be administered once or twice daily. Its subjective-effects profile is different to that of methylphenidate and atomoxetine is not associated with abuse or diversion; it is therefore not a controlled substance in the US. This also means repeat prescriptions during long-term treatment can be more conveniently processed. Atomoxetine is an effective and generally well tolerated treatment for adults with ADHD. It is a nonstimulant and is the first ADHD treatment to be approved specifically for adult use based on its efficacy in well controlled adult trials. It can be administered as a single daily dose or split into two evenly divided doses. It carries negligible risk of abuse or diversion and is not a controlled substance. Atomoxetine is a valuable new treatment option for adults with ADHD and is particularly useful in patients who are at risk for substance abuse or who do not wish to take a controlled substance.

Spotlight on atomoxetine in adults with attention-deficit hyperactivity disorder.

Atomoxetine (Strattera) is a selective noradrenaline (norepinephrine) reuptake inhibitor and nonstimulant that has shown greater efficacy than placebo in attention-deficit hyperactivity disorder (ADHD) in adults. In two large, well controlled, 10-week trials in adults with ADHD, improvements in ADHD symptoms, as assessed by investigator- and patient-rated scores, were greater with oral atomoxetine (60, 90 or 120 mg/day) than with placebo. Mean reductions in the total ADHD symptom score on the investigator-rated Conners' Adult ADHD Rating Scale (CAARS) in atomoxetine versus placebo recipients were 28.3% versus 18.1% and 30.1% versus 19.6%, respectively. Mean reductions in the scores on the Clinician Global Impression of Severity Scale, patient-rated CAARS and Wender-Reimherr Adult Attention Deficit Disorder Scale were also significantly greater with atomoxetine than with placebo. Continued efficacy was demonstrated in a noncomparative, 34-week extension phase. Atomoxetine was generally well tolerated in clinical trials; withdrawal rates due to adverse events in atomoxetine- versus placebo-treated patients participating in the two major trials were 7.8% versus 4.3% and 9.3% versus 2.4% (p < 0.05 for the latter trial). Adverse events reported significantly more frequently with atomoxetine than placebo included dry mouth, insomnia, nausea, decreased appetite, constipation, dizziness, sweating, dysuria, sexual problems and palpitations. Modest increases in heart rate and blood pressure were well tolerated and gradually decreased on cessation of treatment. Atomoxetine was not associated with QT interval prolongation. Atomoxetine can be administered once or twice daily. Its subjective-effects profile is different to that of methylphenidate and atomoxetine is not associated with abuse or diversion; it is therefore not a controlled substance in the US. This also means repeat prescriptions during long-term treatment can be more conveniently processed. Atomoxetine is an effective and generally well tolerated treatment for adults with ADHD. It is a nonstimulant and is the first ADHD treatment to be approved specifically for adult use based on its efficacy in well controlled adult trials. It can be administered as a single daily dose or split into two evenly divided doses. It carries negligible risk of abuse or diversion and is not a controlled substance. Atomoxetine is a valuable new treatment option for adults with ADHD and is particularly useful in patients who are at risk for substance abuse or who do not wish to take a controlled substance.

Reinforcing and subjective effects of methylphenidate in humans.

This study assessed the reinforcing and subjective effects of methylphenidate in a group of 35 adults (15 females and 20 males) with no history of drug dependence. A discrete-trial choice procedure was used to assess the reinforcing effects of a single oral dose of methylphenidate selected to produce a moderate subjective response in each subject (range 20-40mg). A number of variables (gender, current and past drug use, personality, and baseline mood and arousal) were examined in an attempt to identify sources of variability in drug response. Methylphenidate was chosen on 28% of occasions. In the group as a whole, methylphenidate had no effect on ratings of drug liking, but did increase ratings indicative of "positive" mood, CNS stimulation and anxiety. Within-subject variability in methylphenidate choice was related to variability in subjective response to the drug across choice trials. Methylphenidate choice was also associated with between-subject differences in prior opioid use and several personality dimensions. When compared with the results of a prior study of the same design with d-amphetamine, these results suggest that methylphenidate produces a somewhat different profile of subjective effects, and may be a less efficacious reinforcer than d-amphetamine.

Discriminative stimulus effects of caffeine and benzphetamine in amphetamine-trained volunteers.

The discriminative stimulus (DS) and subjective effects of caffeine (100 and 300 mg, PO) and benzphetamine (12.5 and 50 mg, PO) were studied in 18 normal human volunteers trained to discriminate between d-amphetamine (10 mg) and placebo. d-Amphetamine increased ratings of drug liking and activity level and produced a profile of subjective effects characteristic of amphetamine and related psychomotor stimulants. The DS effects of d-amphetamine generalized only partially to caffeine and benzphetamine; mean percent d-amphetamine-appropriate responding was 42 and 58 after 100 and 300 mg caffeine, respectively, and 17 and 56 after 12.5 and 50 mg benzphetamine, respectively. Neither dose of caffeine affected ratings of drug liking or activity level, but 300 mg caffeine did produce a profile of subjective effects that partially overlapped with that produced by d-amphetamine. Benzphetamine 50 mg, but not 12.5 mg, increased ratings of drug liking and activity level and produced a profile of subjective effects qualitatively similar to, but weaker than, that produced by d-amphetamine. For both caffeine and benzphetamine, a close relationship was observed between their subjective effects and their ability to substitute for the DS effects of d-amphetamine. These results correspond well with findings obtained from similar studies conducted with laboratory animals, providing further support for the reliability and validity of human drug discrimination paradigms.

Relationship between the discriminative stimulus properties and subjective effects of drugs.

Behavioral pharmacologists have assumed that the properties of drugs that mediate their discriminative stimulus effects are related to aspects of drug actions that result in their subjective effects in humans. The basis of this assumption is examined in this chapter. Evidence to support this assumption includes the formal properties of the learning process involved in acquiring both behaviors. Although the procedures used to train animals to learn a drug discrimination are explicit, an analysis of how humans learn to attach verbal responses to unobservable internal subjective states appears to involve a similar learning paradigm. Additional evidence of the commonality of the two effects is that the results from drug discrimination studies in animals and studies evaluating subjective effects in humans yield similar drug classifications. However, when subjective drug effects are analyzed in more detail, it is clear that the concordance between the two approaches is not always good. On the other hand, when drug discrimination and subjective effects are both measured in humans, an examination of the results generated when individuals respond differently to the same drug indicates that the hypothesis that their discrimination is based upon a profile of subjective effects is supported.