Low Addictive Potential Research Articles

Prediction of Employees’ Addiction Potential Based on Some of the Most Important Psychological Variables: A Discriminant Analysis Study

Background: Drug addiction significantly impacts employee performance, leading to increased absenteeism, reduced productivity, and higher rates of occupational accidents. Therefore, identifying predictive factors for addiction potential is crucial in preventing drug dependence. Objectives: This study aimed to develop a group membership model using discriminant analysis to predict employees' potential for addiction based on key psychological variables. Methods: A correlational study was conducted with a statistical population consisting of all employees working in public departments in Bojnord City, Iran, in 2021 (N = 2,837). A random sample of 303 employees was selected to complete the Iranian Form of the Addiction Potential Scale, the Big Five Inventory, the Cognitive Emotional Regulation Questionnaire, and the Generalized Self-Efficacy Scale. Data analysis was performed using the discriminant analysis method in SPSS software version 23. Results: The findings revealed that employees' addiction potential can be predicted using personality and cognitive variables. The discriminant analysis equation effectively distinguishes employees with high and low addiction potential based on psychological variables, including extroversion, neuroticism, self-efficacy, and cognitive emotional regulation. Conclusions: The study concluded that self-efficacy, cognitive emotional regulation, neuroticism, and extroversion are significant predictors of addiction potential. It is recommended to incorporate these variables into training courses and personnel selection processes for government jobs.

Key Transdermal Patch Using Cannabidiol-Loaded Nanocarriers with Better Pharmacokinetics in vivo.

Cannabidiol (CBD) is a promising therapeutic drug with low addictive potential and a favorable safety profile. However, CBD did face certain challenges, including poor solubility in water and low oral bioavailability. To harness the potential of CBD by combining it with a transdermal drug delivery system (TDDS). This innovative approach sought to develop a transdermal patch dosage form with micellar vesicular nanocarriers to enhance the bioavailability of CBD, leading to improved therapeutic outcomes. A skin-penetrating micellar vesicular nanocarriers, prepared using nano emulsion method, cannabidiol loaded transdermal nanocarriers-12 (CTD-12) was presented with a small particle size, high encapsulation efficiency, and a drug-loaded ratio for CBD. The skin permeation ability used Strat-M™ membrane with a transdermal diffusion system to evaluate the CTD and patch of CTD-12 (PCTD-12) within 24 hrs. PCTD-12 was used in a preliminary pharmacokinetic study in rats to demonstrate the potential of the developed transdermal nanocarrier drug patch for future applications. In the transdermal application of CTD-12, the relative bioavailability of the formulation was 3.68 ± 0.17-fold greater than in the free CBD application. Moreover, PCTD-12 indicated 2.46 ± 0.18-fold higher relative bioavailability comparing with free CBD patch in the ex vivo evaluation. Most importantly, in the pharmacokinetics of PCTD-12, the relative bioavailability of PCTD-12 was 9.47 ± 0.88-fold higher than in the oral application. CTD-12, a transdermal nanocarrier, represents a promising approach for CBD delivery, suggesting its potential as an effective transdermal dosage form.

Search for the Natural Remedies for the Treatment of Dry Cough

Search for the Natural Remedies for the Treatment of Dry Cough

Abstract 15735: Acquired Long-QT Syndrome Due to Excessive Loperamide Use

Background: Loperamide is an over-the-counter opioid used primarily to treat diarrhea. Toxicity is known to predispose patients to life-threatening QT-interval prolongation and ventricular dysrhythmias. Case: A 42 year-old man with a past medical history of palpitations, tobacco use disorder, chronic back pain, and opioid use disorder presented to the hospital for syncope. In the preceding days, he experienced three episodes of palpitations followed by dizziness that would cause him to lose consciousness and fall, lasting five seconds each. He noted a longstanding opioid use history for chronic back pain, initially treated with oxycodone at a maximum dose of 600mg daily with transition to heroin for a total of three months. The patient then self-managed his opioid dependence with loperamide five years prior to admission, initially using doses of 200 mg daily, followed by three years of taking 768mg of loperamide daily. In attempts to avoid known electrophysiologic complications, he co-administered vitamin C (12,000-14,000 mg daily), magnesium citrate (1200mg/day), D3 (4000u daily), fish oil, centrum multivitamin 2 pills daily, and zinc. In the Emergency Department, the patient was given was given intravenous calcium, amiodarone, and magnesium for recurrent pulseless ventricular tachycardia, ultimately defibrillated and converted to junctional bradycardia. He was admitted to the cardiac care unit. Left heart catheterization demonstrated nonobstructive coronary artery disease; transthoracic echocardiogram was only notable for ejection fraction of 45%. He was treated with transvenous pacemaker (TVP) placement with pacing at 100bpm. Because of increasing intensity of opioid withdrawal, TVP was removed and isoproterenol infusion was started, while initiating transition to suboxone for maintenance treatment. Conclusion: This is the highest reported dose of loperamide intoxication as a method to self-manage opioid dependence. Despite low addictive potential, loperamide may be used at higher doses for opioid dependence or its euphoric effects. Treatment of loperamide toxicity should be aimed at reducing the risk of cardiotoxicity and managing withdrawal symptoms during detoxification, given its variable half-life.

Use of methamphetamine and alcohol among people with opioid use disorder and HIV in Vietnam: a qualitative study

BackgroundHeroin use continues to drive HIV transmission in Vietnam, but methamphetamine and alcohol use are growing rapidly and, as in other countries, polysubstance use is widespread. The objective of this study was to understand the interplay between heroin, methamphetamine, and alcohol use among people with opioid use disorder (OUD) and HIV in Vietnam.MethodsWe conducted 44 in-depth, face-to-face qualitative interviews with people with OUD and HIV who participated in the BRAVO trial of buprenorphine versus methadone in five Vietnam HIV clinics. Interviews probed participants’ experiences of heroin, methamphetamine, and alcohol use and their interplay with HIV/OUD treatment. Interviews were professionally transcribed and analyzed using a thematic analysis approach.ResultsOf 44 participants interviewed 42 were male, on average 38.8 years of age, with 30 reporting a history of methamphetamine use and 33 reporting a history of alcohol use. Several themes emerged: 1) Methamphetamine and alcohol were perceived to have lower addiction potential than heroin 2) Social settings were key facilitators of alcohol and methamphetamine use 3) Some participants, but not all, used methamphetamine to help quit heroin 4) Consuming alcohol blunted the effects of heroin, while paradoxically serving as a catalyst for heroin use 5) Use of methamphetamine was perceived by many participants to be incompatible with treatment for HIV.ConclusionsParticipant experiences reflected a significant impact of polysubstance use on treatment of HIV and OUD. Patterns of polysubstance use are subject to common preconceptions of alcohol and methamphetamine as having a low addictive potential, and these substances are deeply enmeshed in the social life of many people with OUD in Vietnam. Interventions to address complex social norms and potential harms of polysubstance use are urgently needed as the population of people receiving medication for OUD (MOUD) increases in Vietnam and globally.Trial registrationBRAVO - NCT01936857, September 2013.

Nicotine delivery and relief of craving after consumption of European JUUL e-cigarettes prior and after pod modification

The emergence of e-cigarettes on the consumer market led to a tremendous rise in e-cigarette consumption among adolescents in the United States. The success of JUUL and other pod systems was linked to its high nicotine delivery capacity. In compliance with the European Tobacco Product directive, liquid nicotine contents in the European JUUL variants are limited to 20 mg/mL or below. A short time after launching the initial version in Europe, JUUL pods have been modified in terms of the wick material used. This modification has been demonstrated previously to lead to an elevated aerosol generation, consequently, to a larger amount of nicotine per puff generated. The present study was designed to assess whether the mentioned differences between the “initial” and “modified” JUUL versions may cause a significant difference during consumption, and how nicotine delivery compares with tobacco cigarettes. In this single-center three-arm study, nicotine pharmacokinetics and influence on urge to smoke/vape were compared for tobacco cigarettes, the “initial” version of the European JUUL, and the “modified” version of the European JUUL. Participants, 15 active smokers and 17 active e-cigarette users, were instructed to consume their study product according to a pre-directed puffing protocol. Venous blood was sampled for nicotine analysis to cover the acute phase and the first 30 min after starting. Nicotine delivery and the reduction of urge to smoke/vape upon usage of both European JUUL variants were lower in comparison to tobacco cigarettes. This suggests a lower addictive potential. Modification of the pod design did not result in significant differences at the first ten puffs, as confirmed by a vaping machine experiment. Apparently, the limitations by the initially used wick material only come into effect after longer usage time.

Neuroactive Type-A γ-Aminobutyric Acid Receptor Allosteric Modulator Steroids from the Hypobranchial Gland of Marine Mollusk, Conus geographus.

In a program to identify pain treatments with low addiction potential, we isolated five steroids, conosteroids A-E (1-5), from the hypobranchial gland of the mollusk Conus geographus. Compounds 1-5 were active in a mouse dorsal root ganglion (DRG) assay that suggested that they might be analgesic. A synthetic analogue 6 was used for a detailed pharmacological study. Compound 6 significantly increased the pain threshold in mice in the hot-plate test at 2 and 50 mg/kg. Compound 6 at 500 nM antagonizes type-A γ-aminobutyric acid receptors (GABAARs). In a patch-clamp experiment, out of the six subunit combinations tested, 6 exhibited subtype selectivity, most strongly antagonizing α1β1γ2 and α4β3γ2 receptors (IC50 1.5 and 1.0 μM, respectively). Although the structures of 1-6 differ from those of known neuroactive steroids, they are cell-type-selective modulators of GABAARs, expanding the known chemical space of neuroactive steroids.

Relative addictive potential of opioid analgesic agents.

Opioid overdoses and deaths continue to be a problem in the USA with a significant portion related to prescribed opioid analgesic agents. The role of pharmacogentic factors in opioid addiction is an active area of research. While all opioid analgesic agents have some addictive potential, it is clear that there are some with greater addictive potential. Oxycodone is the most widely abused opioid analgesic and it appears to predispose to chronic use with high likability by users. Fentanyl and hydromorphone are both very lipophilic allowing rapid penetration into the CNS, but are not rated as highly as other agents. Providers should consider the risk of addiction with the opioids they prescribe and give those with a lower addictive potential.

The role of eugeroics in the treatment of affective disorders.

Eugeroics are a relatively new class of wakefulness-promoting agents. Thegroup includes adrafinil, modafinil and armodafinil. Modafinil is the most widely used and the best studied agent. Indications for the use of modafinil include the treatment of narcolepsy, shift-work sleep disorders and excessive daytime sleepiness associated with obstructive sleep apnea. Many studies show the utility of modafinil and armodafinil in the treatment of depression - both in monotherapy andas potentiation therapy if needed. Modafinil has proven to be effective in the treatment of residual symptoms of unipolar and bipolar depression such as fatigue, excessive sleepiness and some cognitive impairment. Research on armodafinil points to its effectiveness mainly in augmentation therapy of depression in the course of bipolar disorder. There are also reports on the effectiveness of eugeroics in special cases - seasonal depression, atypical depression with hyperphagia, apathy in the course of depression or as an isolated symptom, cancer-related fatigue in patients receiving chemotherapy, fatigue and excessive sleepiness in neurological diseases. Eugeroics due to their high selectivity of action in the CNS have a low addictive potential compared with other stimulants. The risk of manic switch is comparable to placebo. In general, they are well-tolerated and safe. The purpose of this paper is to review the literature on the use of eugeroics in the treatment of affective disorders.

Estrogen Regulation of GRK2 Inactivates Kappa Opioid Receptor Signaling Mediating Analgesia, But Not Aversion.

Activation of κ opioid receptors (KORs) produces analgesia and aversion via distinct intracellular signaling pathways, but whether G protein-biased KOR agonists can be designed to have clinical utility will depend on a better understanding of the signaling mechanisms involved. We found that KOR activation produced conditioned place aversion and potentiated CPP for cocaine in male and female C57BL/6N mice. Consistent with this, males and females both showed arrestin-mediated increases in phospho-p38 MAPK following KOR activation. Unlike in males, however, KOR activation had inconsistent analgesic effects in females and KOR increased Gβγ-mediated ERK phosphorylation in males, but not females. KOR desensitization was not responsible for the lack of response in females because neither Grk3 nor Pdyn gene knock-out enhanced analgesia. Instead, responsiveness was estrous cycle dependent because KOR analgesia was evident during low estrogen phases of the cycle and in ovariectomized (OVX) females. Estradiol treatment of OVX females suppressed KOR-mediated analgesia, demonstrating that estradiol was sufficient to blunt Gβγ-mediated KOR signals. G protein-coupled receptor kinase 2 (GRK2) is known to regulate ERK activation, and we found that the inhibitory, phosphorylated form of GRK2 was significantly higher in intact females. GRK2/3 inhibition by CMPD101 increased KOR stimulation of phospho-ERK in females, decreased sex differences in KOR-mediated inhibition of dopamine release, and enhanced mu opioid receptor and KOR-mediated analgesia in females. In OVX females, estradiol increased the association between GRK2 and Gβγ. These studies suggest that estradiol, through increased phosphorylation of GRK2 and possible sequestration of Gβγ by GRK2, blunts G protein-mediated signals.SIGNIFICANCE STATEMENT Chronic pain disorders are more prevalent in females than males, but opioid receptor agonists show inconsistent analgesic efficacy in females. κ opioid receptor (KOR) agonists have been tested in clinical trials for treating pain disorders based on their analgesic properties and low addictive potential. However, the molecular mechanisms underlying sex differences in KOR actions were previously unknown. Our studies identify an intracellular mechanism involving estradiol regulation of G protein-coupled receptor kinase 2 that is responsible for sexually dimorphic analgesic responses following opioid receptor activation. Understanding this mechanism will be critical for developing effective nonaddictive opioid analgesics for use in women and characterizing sexually dimorphic effects in other inhibitory G protein-coupled receptor signaling responses.

The epidemiology of 5-methoxy- N, N-dimethyltryptamine (5-MeO-DMT) use: Benefits, consequences, patterns of use, subjective effects, and reasons for consumption.

5-Methoxy- N,N-dimethyltryptamine (5-MeO-DMT) is a psychoactive compound found in several plants and in high concentrations in Bufo alvarius toad venom. Synthetic, toad, and plant-sourced 5-MeO-DMT are used for spiritual and recreational purposes and may have psychotherapeutic effects. However, the use of 5-MeO-DMT is not well understood. Therefore, we examined patterns of use, motivations for consumption, subjective effects, and potential benefits and consequences associated with 5-MeO-DMT use. Using internet-based advertisements, 515 respondents ( Mage=35.4. SD=11.7; male=79%; White/Caucasian=86%; United States resident=42%) completed a web-based survey. Most respondents consumed 5-MeO-DMT infrequently (<once/year), for spiritual exploration, and had used less than four times in their lifetime. The majority (average of 90%) reported moderate-to-strong mystical-type experiences ( Mintensity=3.64, SD=1.11; range 0-5; e.g., ineffability, timelessness, awe/amazement, experience of pure being/awareness), and relatively fewer (average of 37%) experienced very slight challenging experiences ( Mintensity=0.95, SD=0.91; range 0-5; e.g., anxiousness, fear). Less than half (39%) reported repeated consumption during the same session, and very few reported drug craving/desire (8%), or legal (1%), medical (1%), or psychiatric (1%) problems related to use. Furthermore, of those who reported being diagnosed with psychiatric disorders, the majority reported improvements in symptoms following 5-MeO-DMT use, including improvements related to post-traumatic stress disorder (79%), depression (77%), anxiety (69%), and alcoholism (66%) or drug use disorder (60%). Findings suggest that 5-MeO-DMT is used infrequently, predominantly for spiritual exploration, has low potential for addiction, and might have psychotherapeutic effects. Future research should examine the safety and pharmacokinetics of 5-MeO-DMT administration in humans using rigorous experimental designs.

Modafinil Dependence: A Case with Attention-Deficit/Hyperactivity Disorder.

Modafinil is generally known as a drug with low addiction potential. There are few case reports in the literature demonstrating that Modafinil, stated being capable of diminishing symptoms of attention deficit/hyperactivity disorder (ADHD), causes addiction. In the present article a Modafinil addicted ADHD case, consuming usurious doses (5,000 mg/per day) of Modafinil is presented. The case presented to our psychiatry outpatient clinic due to: requirement of in taking high dose Modafinil in order to achieve the initial effects, difficulty in obtaining the drug, irritability, anxiousness, sleep irregularities, fatigue and unpleasant vivid dreams when he did not use the drug. It was realized that the patient, himself increased doses of Modafinil incrementally, in order to keep its effects on attention symptoms at the same level. It has to be kept in mind that ADHD patients can develop Modafinil addiction. It is necessary to carry out systemic studies on this subject.

Characteristics of "American Snus" and Swedish Snus Products for Sale in Massachusetts, USA.

Snus may present lower health risks than cigarettes, but its harm reduction potential may be undermined if used dually with cigarettes. The likelihood of exclusive snus use compared with dual use may depend in part on the capacity of snus to deliver nicotine in doses that are satisfactory to smokers. We examined characteristics of "American snus" products, including nicotine levels, and compared to snus products that are more typical of Sweden. Tobacco industry reports for snus products submitted to the Massachusetts Department of Public Health for the year 2014 were used to assess moisture (%), pH, total nicotine, and unionized (free) nicotine (both mg/g and percent of total). A total of 14 ("American") snus products made by American manufacturers Philip Morris USA (n = 6), R.J. Reynolds Tobacco Company (n = 6), and US Smokeless Tobacco Company (n = 2), were compared with Swedish-style ("Swedish") snus products (n = 10) made by Swedish Match North America. Compared with Swedish snus, American snus brands contained significantly lower concentrations of unionized nicotine (median: 0.52 mg/g vs. 6.52 mg/g; p < .001) and proportion of unionized nicotine (median: 3.17% vs. 81.8%; p < .001). American snus brands also had significantly lower pH (median: 6.54 vs. 8.68; p < .001) and moisture (median: 30.3% vs. 53.4%; p < .001). Swedish-made snus has higher unionized nicotine, measured by concentration and proportion of total nicotine, compared with snus products made by American manufacturers. These findings suggest that American snus products have lower addiction potential than Swedish snus, and may be more likely to be used dually with cigarettes than as a sole source of nicotine. American snus products contain significantly lower unionized nicotine, lower pH, and lower moisture, compared with Swedish snus products. Snus addiction potential and patterns of usage, including co-use with cigarettes, may differ between American and Swedish snus products due to differences in snus product characteristics.

Salvia divinorum: An overview of the usage, misuse, and addiction processes.

Salvia divinorum, a sage plant with leaves that can produce a psychoactive high, has been used for hundreds of years for its psycho-mimetic effects in religious rituals in South America. Salvia has now become popular mainly with adolescents and young adults for the short-lived relatively pleasant experiences many consider a "legal high" and its ready availability through Internet purchases. The main (psycho)active compound in salvia is Salvinorin A, a potent κ-opioid agonist and although the short and long-term effects have not been examined in sufficient detail, it is widely believed to have low addictive potential and low toxicity. Recent findings, however, seem to suggest that Salvinorin A can precipitate psychiatric symptoms and negatively affect cognition. Its ready availability and increasingly widespread use requires clinicians to have knowledge and awareness of its effects.

Design, synthesis and biological evaluation of N-phenylalkyl-substituted tramadol derivatives as novel μ opioid receptor ligands

Tramadol is an atypical opioid analgesic with low potential for tolerance and addiction. However, its opioid activity is much lower than classic opiates such as morphine. To develop novel analgesic and further explore the structure activity relationship (SAR) of tramadol skeleton. Based on a three-dimensional (3D) structure superimposition and molecular docking study, we found that M1 (the active metabolite of tramadol) and morphine have common pharmacophore features and similar binding modes at the μ opioid receptor in which the substituents on the nitrogen atom of both compounds faced a common hydrophobic pocket formed by Trp2936.48 and Tyr3267.43. In this study, N-phenethylnormorphine was docked to the μ opioid receptor. It was found that the N-substituted group of N-phenethylnormorphine extended into a hydrophobic pocket formed by Trp2936.48 and Tyr3267.43. This hydrophobic interaction may contribute to the improvement of its opioid activities as compared with morphine. The binding modes of M1, morphine and N-phenethylnormorphine overlapped, indicating that the substituent on the nitrogen atoms of the three compounds may adopt common orientations. A series of N-phenylalkyl derivatives from the tramadol scaffold were designed, synthesized and assayed in order to generate a new type of analgesics. As a result, compound 5b was identified to be an active candidate from these compounds. Furthermore, the binding modes of 5b and morphine derivatives in the μ opioid receptor were comparatively studied. Unlike morphine-derived structures in which bulky N-substitution is associated with improved opioid-like activities, there seems to be a different story for tramadol, suggesting the potential difference of SAR between these compounds. A new type of interaction mechanism in tramadol analogue (5b) was discovered, which will help advance potent tramadol-based analgesic design.

Cannabinoid replacement therapy (CRT): Nabiximols (Sativex) as a novel treatment for cannabis withdrawal.

Cannabis is a common recreational drug that is generally considered to have low addictive potential. However, an increasing number of cannabis users are seeking treatment for dependence on the drug. There is interest in using agonist (substitution) pharmacotherapies to treat cannabis dependence and here we outline a novel approach involving a buccal spray (nabiximols) that contains tetrahydrocannabinol (THC) and cannabidiol (CBD). We review recent research with nabiximols and highlight findings relevant to clinical practice.

Evaluation of the Effect of Modafinil on Cognitive Functions in Patients with Idiopathic Hypersomnia with P300.

BackgroundModafinil is a well-tolerated psychostimulant drug with low addictive potential that is used to treat patients with narcolepsy and other excessive sleepiness. Whereas favorable effects of modafinil on cognitive functions have been shown in a large number of studies, there are very few reports presenting the effects of modafinil electrophysiologically. The aim of this study was to investigate the effects of modafinil on auditory P300 latency and amplitude electrophysiologically.Material/MethodsEighteen patients (age range: 16–48 years) with a diagnosis of idiopathic hypersomnia (IH) were included in the present study. As a standard treatment, 200 mg/day modafinil was administered to each patient. The P300 auditory test was performed for each patient before and at the end of 1 week of modafinil treatment.ResultsAfter 1 week of modafinil treatment, mean P300 latencies (at all electrode sites) were significantly lower than the latencies before the treatment (P values for Fz, Cz and Pz recording sites were 0.039, 0.002, and 0.004, respectively). An increase in the P300 amplitudes was detected only at the Fz recording site, but not at Cz or Pz recording sites (P values for Fz, Cz, and Pz recording sites were 0.014, 0.100, and 0.05, respectively).ConclusionsOne week of modafinil treatment improved the cognitive performance, alertness, and executive functions in IH patients. Our electrophysiologically obtained findings provide further confirmation for previous reports in which modafinil has been shown to exert favorable effects on cognitive performance, alertness, and executive functions.

High in the Nursing Home

High in the Nursing Home

Dose-Related Behavioral, Subjective, Endocrine, and Psychophysiological Effects of the κ Opioid Agonist Salvinorin A in Humans

Salvia divinorum (Salvia) is an increasingly popular recreational drug amongst adolescents and young adults. Its primary active ingredient, Salvinorin A (SA)-a highly selective agonist at the κ opiate receptor-is believed to be one of the most potent naturally occurring hallucinogens. However, there is little experimental data on the effects of SA in humans. In a 3-day, double-blind, randomized, crossover, counterbalanced study, the behavioral, subjective, cognitive, psychophysiological, and endocrine effects of 0 mg, 8 mg, and 12 mg of inhaled SA were characterized in 10 healthy individuals who had previously used Salvia. SA produced psychotomimetic effects and perceptual alterations, including dissociative and somaesthetic effects, increased plasma cortisol and prolactin, and reduced resting electroencephalogram spectral power. The SA administration was associated with a rapid increase of its levels in the blood. SA did not produce euphoria, cognitive deficits, or changes in vital signs. The effects were transient and not dose-related. SA administration was very well-tolerated without acute or delayed adverse effects. SA produced a wide range of transient effects in healthy subjects. The perceptual altering effects and lack of euphoric effects would explain its intermittent use pattern. Such a profile would also suggest a low addictive potential similar to other hallucinogens and consistent with κ opiate receptor agonism. Further work is warranted to carefully characterize a full spectrum of its effects in humans, to elucidate the underlying mechanisms involved, and to explore the basis for individual variability in its effects.

LAMIVUDINE-ARTESUNATE CO ADMINISTRATION ALTERS PIROXICAM MEDIATED ANALGESIA IN MICE

Lamivudine-Artesunate co-administration is common in HIV-malaria settings, as well as in prophylaxis from occupational HIV exposure and presumptive malaria treatment. Pain is a symptom often associated with malaria and HIV which is usually treated with piroxicam due to availability, affordability, and low addiction potential. This study evaluated possible analgesic effects of lamivudine and artesunate, and also the effect of lamivudine-artesunate co-administration on piroxicam mediated analgesia in mice using acetic acid-induced writhing method. Animals received 21 day intraperitoneal treatments with vehicle, lamivudine, artesunate or lamivudine/artesunate co-administration. The result showed that artesunate possessed analgesic properties, and also showed that piroxicam mediated analgesia was significantly reduced (p 0.05) in the presence of concomitant lamivudine-artesunate treatment. This data suggests the need for caution and possible alternate analgesics while on lamivudine-artesunate therapy in order to effectively alleviate pain, when this is desired in lamivudine-artesunate co administration.