Addiction
Cannabidiol Reduced the Severity of Gastrointestinal Symptoms of Opioid Withdrawal in Male and Female Mice
Rhianne L. Scicluna, Bianca B. Wilson, Samuel H. Thelaus, Jonathon C. Arnold, Iain S. McGregor, and Michael T. Bowen (December 2022)
Opioid withdrawal is a powerful driver of drug-seeking behavior as relief from this aversive state through drug-taking is a strong negative reinforcer. There are currently limited treatment options available for opioid withdrawal and cannabidiol (CBD) has been identified as a potential novel therapeutic. This study explored the efficacy and dose dependency of CBD for reducing the severity of naloxone-precipitated and spontaneous oxycodone withdrawal (PW and SW, respectively) in male and female mice.
The magnitude of effects on the gastrointestinal symptoms, their consistency across PW and SW, and both sexes, alongside the availability of CBD for clinical use, suggest further exploration of the potential for CBD to treat these symptoms could be justified.
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Recreational Marijuana Laws and the Misuse of Prescription Opioids: Evidence from National Survey on Drug Use and Health Microdata
Mir M. Ali, Chandler McClellan, Ryan Mutter, Daniel I. Rees (November 2022)
Several studies have concluded that legalizing medical marijuana can reduce deaths from opioid overdoses. Drawing on micro data from the National Survey on Drug Use and Health, a survey uniquely suited to assessing patterns of substance use, we examine the relationship between recreational marijuana laws (RMLs) and the misuse of prescription opioids. Using a standard difference-in-differences (DD) regression model, we find that RML adoption reduces the likelihood of frequently misusing prescription opioids such as OxyContin, Percocet, and Vicodin. However, using a two-stage procedure designed to account for staggered treatment and dynamic effects, the DD estimate of relationship between RML adoption and the likelihood of frequently misusing prescription opioids becomes positive. Although event study estimates suggest that RML adoption leads to a decrease in the frequency of prescription opioid abuse, this effect appears to dissipate after only 2 or 3 years.
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CBD-Mediated Regulation of Heroin Withdrawal-Induced Behavioural And Molecular Changes In Mice
Francisco Navarrete, Ani Gasparyan, Jorge Manzanares (February 2022)
Cannabidiol (CBD) may represent a promising therapeutic tool for treating opioid use disorder (OUD). This study was aimed to evaluate the effects of CBD on the behavioural and gene expression alterations induced by spontaneous heroin withdrawal. Thirty hours after cessation of 8-day heroin treatment (5, 10, 20 and 40 mg·kg−1/12 h; s.c.), spontaneous heroin withdrawal was evaluated in CD1 male mice. The effects of CBD (5, 10 and 20 mg·kg−1; i.p.) on withdrawal-related behaviour were evaluated by measuring anxiety-like behaviour, motor activity and somatic signs.
The results suggest that CBD alleviates spontaneous heroin withdrawal and normalizes the associated gene expression changes. Future studies are needed to determine the relevance of CBD as a potential therapeutic tool for the treatment of heroin withdrawal.
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Cannabidiol Prevents Several of the Behavioral Alterations Related to Cocaine Addiction in Mice
Juan Carlos Ledesma, Carmen Manzanedo, Maria A. Aguilar (March 2021)
Overall, our data endorse CBD as a promising treatment of cocaine addiction, at least at the pre-clinical level. CBD may be an effective pharmacological tool in the management of some of the behavioral alterations seen in CUD, in particular by avoiding relapse to cocaine consumption in addicted patients and reducing the memory disturbances evoked by chronic consumption of this drug. Moreover, the fact that CBD blocks cocaine-induced locomotor stimulation in mice, and considering that this effect is mediated by the same molecular mechanisms involved in cocaine addiction, we believe that CBD can prevent the development of cocaine dependence. Future pre-clinical studies should evaluate in more depth the efficacy of CBD to revert other behavioral outcomes related to CUD.
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Cannabidiol Prevents Amphetamine Relapse and Modulates D1- and D2-Receptor Levels in Mesocorticolimbic Brain Areas of Rats
Vinicia Garzella Metz, Jessica Leandra Oliveira da Rosa, Domenika Rubert Rossato, Laura Hautrive Milanesi, Marilise Escobar Burger, Camila Simonetti Pase (May 2021)
Amphetamine (AMPH) is an addictive psychostimulant highly used worldwide and its consumption is related to neurotoxic effects. Currently, there is no pharmacotherapy approved for treating AMPH or other psychostimulant drug addiction. Different studies have shown promising properties of cannabidiol (CBD) for treating many neurological and psychiatric diseases, and recently, CBD is being considered a potential strategy for the treatment of drug addiction disorders. Thus, we investigated possible CBD beneficial effects on relapse symptoms following AMPH re-exposure considering drug relapse is the most difficult clinical factor to control during addiction treatment.
The current findings give evidence about CBD-induced AMPH-relapse prevention, which may be linked to dopaminergic mesocorticolimbic system modulation. Although future and clinical studies are needed, our outcomes show that CBD may be a useful alternative to prevent AMPH relapse.
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Reducing Effect of Cannabidiol on Alcohol Self-Administration in Sardinian Alcohol-Preferring Rats
Paola Maccioni, Jessica Bratzu, Mauro A. M. Carai, Giancarlo Colombo, and Gian Luigi Gessa (March 2021)
Cannabidiol (CBD) is a major cannabinoid extracted from Cannabis sativa with no abuse potential. Data from recent rodent studies suggest that amelioration of alcohol-motivated behaviors may be one of the numerous pharmacological effects of CBD. This study was designed to contribute to this research, assessing the effect of CBD on operant oral alcohol self-administration in selectively bred Sardinian alcohol-preferring (sP) rats, a validated animal model of excessive alcohol consumption. In addition, this study investigated the effect of CBD on operant self-administration of a highly palatable chocolate solution in Wistar rats.
Under the FR schedule, treatment with doses of CBD ≥12.5 mg/kg markedly reduced lever responding for alcohol and amount of self-administered alcohol. Under the PR schedule, treatment with CBD produced a slight tendency toward a decrease in lever responding and breakpoint for alcohol. Finally, no dose of CBD affected lever responding for the chocolate solution and amount of self-administered chocolate solution.
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Cannabidiol Efficiently Suppressed the Acquisition and Expression of Methamphetamine-Induced Conditioned Place Preference in the Rat
Mahsa Enooshe, Kiana Nouri, Saeideh Karimi-Haghighi, Zahra Mousavi, Abbas Haghparast (February 2021)
Methamphetamine (MET) is one of the most prevalently abused psychostimulants in the world with drastic repercussions. Several studies emphasized the inhibitory effect of Cannabidiol (CBD) on the reward properties of psychostimulants. The current investigation utilized conditioned place preference (CPP) to assay CBD's impact on MET's reward characteristic, including acquisition and expression phases of MET-induced CPP.
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Neuroprotective Effect of Chronic Administration of Cannabidiol During the Abstinence Period on Methamphetamine-induced Impairment of Recognition Memory in the Rats
Razavi, Yasaman; Shabani, Ronak; Mehdizadeh, Mehdi; Haghparast, Abbas (June 2020)
Neuropsychiatric disorders, such as addiction, are associated with cognitive impairment, including learning and memory deficits. Previous research has demonstrated that the chronic use of methamphetamine (METH) induces long-term cognitive impairment and cannabidiol (CBD), as a neuroprotectant, can reverse spatial memory deficits induced by drug abuse. The study aimed to evaluate the effect of CBD on METH-induced memory impairment in rats chronically exposed to METH (CEM).
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If you proceed to article you will be leaving the CB1 Capital Management website to access a website hosted by a party unrelated to CB1 Capital Management. CB1 Capital Management assumes no responsibility for the accuracy of any of these studies nor does CB1 assume any obligation to update any of these studies based on subsequent research.
Cannabinoids and the Microbiota‐Gut‐Brain‐Axis: Emerging Effects of Cannabidiol and Potential Applications to Alcohol Use Disorders
Hollis Karoly, Raeghan Mueller, Cinnamon Bidwell and Kent Hitchison (December 2019)
The endocannabinoid system (ECS) has emerged in recent years as a potential treatment target for alcohol use disorders (AUD). In particular, the non‐psychoactive cannabinoid cannabidiol (CBD) has shown preclinical promise in ameliorating numerous clinical symptoms of AUD. There are several proposed mechanism(s) through which cannabinoids (and CBD in particular) may confer beneficial effects in the context of AUD. First, CBD may directly impact specific brain mechanisms underlying AUD to influence alcohol consumption and the clinical features of AUD. Second, CBD may influence AUD symptoms through its actions across the digestive, immune, and central nervous systems, collectively known as the microbiota‐gut‐brain‐axis (MGBA). Notably, emerging work suggests that alcohol and cannabinoids exert opposing effects on the MGBA. Alcohol is linked to immune dysfunction (e.g., chronic systemic inflammation in the brain and periphery) as well as disturbances in gut microbial species (microbiota) and increased intestinal permeability. These MGBA disruptions have been associated with AUD symptoms such as craving and impaired cognitive control.
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If you proceed to article you will be leaving the CB1 Capital Management website to access a website hosted by a party unrelated to CB1 Capital Management. CB1 Capital Management assumes no responsibility for the accuracy of any of these studies nor does CB1 assume any obligation to update any of these studies based on subsequent research.
Cannabis Use During Methadone Maintenance Treatment for Opioid Use Disorder: A Systematic Review and Meta-analysis
Heather McBrien, Candice Luo, BHSc, Nitika Sanger, BHSc, Laura Zielinski, MSc, Meha Bhatt, MSc, Xi Ming Zhu, MBBS, David C. Marsh, MD, Lehana Thabane, PhD MSc, Zainab Samaan, MBChB PhD (November 2019)
Background: Rates of cannabis use among patients receiving methadone maintenance therapy are high, and cannabis use may be associated with outcomes of methadone maintenance therapy. We examined the effect of cannabis use on opioid use in patients receiving methadone maintenance therapy to test the hypothesis that cannabis use is associated with a reduction in opioid use.
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Potential of Cannabinoid Receptor Ligands as Treatment for Substance Use Disorders
Ewa Galaj and Zheng-Xiong Xi (October 2019)
Substance use disorder (SUD) is a major public health crisis worldwide, and effective treatment options are limited. During the past 2 decades, researchers have investigated the impact of a variety of pharmacological approaches to treat SUD, one of which is the use of medical cannabis or cannabinoids. Significant progress was made with the discovery of rimonabant, a selective CB1 receptor (CB1R) antagonist (also an inverse agonist), as a promising therapeutic for SUDs and obesity.
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If you proceed to article you will be leaving the CB1 Capital Management website to access a website hosted by a party unrelated to CB1 Capital Management. CB1 Capital Management assumes no responsibility for the accuracy of any of these studies nor does CB1 assume any obligation to update any of these studies based on subsequent research.
Reduced Urinary Opioid Levels from Pain Management Patients Associated with Marijuana Use
Melissa M Goggin, Breane J Shahriar, Andy Stead and Gregory C Janis (September 2019)
Marijuana use has been postulated to modulate opioid use, dependence and withdrawal. Broad target drug testing results provide a unique perspective to identify any potential interaction between marijuana use and opioid use. Materials & methods: Using a dataset of approximately 800,000 urine drug test results collected from pain management patients of a time from of multiple years, creatinine corrected opioid levels were evaluated to determine if the presence of the primary marijuana marker 11-nor-carboxy-tetrahydrocannabinol (THC-COOH) was associated with statistical differences in excreted opioid concentrations. Results & conclusion: For each of the opioids investigated (codeine, morphine, hydrocodone, hydromorphone, oxycodone, oxymorphone, fentanyl and buprenorphine), marijuana use was associated with statistically significant lower urinary opiate levels than in samples without indicators of marijuana use.
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If you proceed to article you will be leaving the CB1 Capital Management website to access a website hosted by a party unrelated to CB1 Capital Management. CB1 Capital Management assumes no responsibility for the accuracy of any of these studies nor does CB1 assume any obligation to update any of these studies based on subsequent research.
State Drug Policy Effectiveness: Comparative Policy Analysis of Drug Overdose Mortality
Jarrod Olson, Po-Hsu Allen Chen, Marissa White, Nicole Brennan and Ning Gong (September 2019)
Opioid overdose rates have reached an epidemic level and state-level policy innovations have followed suit in an effort to prevent overdose deaths. State-level drug law is a set of policies that may reinforce or undermine each other, and analysts have a limited set of tools for handling the policy collinearity using statistical methods. This paper uses a machine learning method called hierarchical clustering to empirically generate "policy bundles" by grouping states with similar sets of policies in force at a given time together for analysis in a 50-state, 10-year interrupted time series regression with drug overdose deaths as the dependent variable. Policy clusters were generated from 138 binomial variables observed by state and year from the Prescription Drug Abuse Policy System. Clustering reduced the policies to a set of 10 bundles. The approach allows for ranking of the relative effect of different bundles and is a tool to recommend those most likely to succeed. This study shows that a set of policies balancing Medication Assisted Treatment, Naloxone Access, Good Samaritan Laws, Medication Assisted Treatment, Prescription Drug Monitoring Programs and legalization of medical marijuana leads to a reduced number of overdose deaths, but not until its second year in force.
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State Marijuana Laws and Opioid Overdose Mortality
Stanford Chihuri and Guohua Li (September 2019)
Legalizing marijuana might contribute to a modest reduction in opioid prescriptions. Evidence about the effect of marijuana legalization on opioid overdose mortality is inconsistent and inconclusive. If any, the effectiveness of state marijuana laws in reducing opioid overdose mortality appears to be rather small and limited to states with operational marijuana dispensaries. It remains unclear whether the presumed benefit of legalizing marijuana in reducing opioid-related harms outweighs the policy’s externalities, such as its impact on mental health and traffic safety.
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First Study of Safety and Tolerability of 3,4-Methylenedioxymethamphetamine (MDMA)-assisted Psychotherapy in Patients with Alcohol Use Disorder: Preliminary Data on the First Four Participants
Ben Sessa, Chloe Sakal, Steve O’Brien and David Nutt (July 2019)
We present the preliminary data in an ongoing open-label safety and tolerability proof of concept study exploring the potential role for 3,4-methylenedioxymethamphetamine (MDMA)-assisted psychotherapy in treating patients with alcohol use disorder. At this stage, seven participants have completed the full 8-week MDMA-assisted psychotherapy course, including two therapy sessions each with MDMA. This paper focuses on the safety and tolerability of the therapeutic course for the first four participants to complete treatment. Longer-term outcomes of drinking behaviour will be presented later when the full project data are published. Results show all four participants have successfully tolerated the treatment. There have been no serious adverse events related to MDMA, no unexpected physiological responses to the MDMA sessions or changes to blood results or electrocardiograms, measured before and after the 8-week course. We conclude that the treatment is well- tolerated and are making plans to expand the project into a randomised placebo-controlled study.
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Nabiximols for the Treatment of Cannabis Dependence: A Randomized Clinical Trial
Nicholas Lintzeris, MBBS, PhD; Anjali Bhardwaj, PhD and Llewellyn Mills, PhD (July 2019)
Question: Is cannabinoid agonist treatment, in combination with psychosocial services, a safe and efficacious approach to reducing illicit cannabis use in patients with cannabis dependence who are seeking treatment? Findings: In this randomized clinical trial of 128 participants, a 12-week course of nabiximols, a combination of tetrahydrocannabinol and cannabidiol, resulted in significantly fewer days of illicit cannabis use compared with placebo, and was well tolerated by participants. Meaning: The use of cannabinoid agonist medication appears to be a promising addition to the treatment of patients with cannabis dependence.
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Cannabidiol for the Reduction of Cue-Induced Craving and Anxiety in Drug-Abstinent Individuals With Heroin Use Disorder: A Double-Blind Randomized Placebo-Controlled Trial
Yasmin L. Hurd, Sharron Spriggs, Julia Alishayev, Gary Winkel, Kristina Gurgov, Chris Kudrich, Anna M. Oprescu and Edwin Salsitz (May 2019)
Despite the staggering consequences of the opioid epidemic, limited nonopioid medication options have been developed to treat this medical and public health crisis. This study investigated the potential of cannabidiol (CBD), a nonintoxicating phytocannabinoid, to reduce cue-induced craving and anxiety, two critical features of addiction that often contribute to relapse and continued drug use, in drug-abstinent individuals with heroin use disorder.
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If you proceed to article you will be leaving the CB1 Capital Management website to access a website hosted by a party unrelated to CB1 Capital Management. CB1 Capital Management assumes no responsibility for the accuracy of any of these studies nor does CB1 assume any obligation to update any of these studies based on subsequent research.
Endocannabinoid-Enhanced “Liking” in Nucleus Accumbens Shell Hedonic Hotspot Requires Endogenous Opioid Signals
Marci R. Mitchell, Kent C. Berridge, and Stephen V. Mahler (July 2018)
Stimulating either endogenous cannabinoids or opioids within a restricted dorsomedial “hedonic hotspot” in nucleus accumbens (NAc) shell enhances hedonic impact, or “liking” reactions to sweet tastes. In this study, we probed within this hotspot the relationship between endocannabinoid and opioid signals in hedonic enhancement. These results elaborate our understanding of the mechanisms of hedonic processing of food rewards, and may also carry implications more generally for how opioid and cannabinoid drugs interact to generate natural pleasures, or drug-induced euphoria.
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Cannabidiol Reverses Attentional Bias to Cigarette Cues in a Human Experimental Model of Tobacco Withdrawal.
Hindocha C, Freeman TP, Grabski M, Stroud JB, Crudgington H, Davies AC, Das RK, Lawn W, Morgan CJA, Curran HV (May 2018)
A single 800mg oral dose of cannabidiol (CBD) reduced the salience and pleasantness of cigarette cues, compared with placebo, after overnight cigarette abstinence in dependent smokers. CBD did not influence tobacco craving or withdrawal or any subjectively rated side-effects.
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Acute and Chronic Modulation of Striatal Endocannabinoid‐mediated Plasticity by Nicotine
Louise Adermark, Julia Morud, Amir Lotfi, Mia Ericson, Bo Söderpalm (January 2018)
Drug addiction is a chronic relapsing disorder that involves progressive adaptations of cortico‐striatal networks (Yin, Ostlund, & Balleine 2008; Belin et al. 2009; Belin et al. 2013; Adermark et al. 2016), and the data presented here suggest that the eCB system might play a role in mediating these transformations. Even though no causal relationship with behavioral transformations was assessed in this study, it is possible that nicotine‐induced facilitation of eCB signaling could promote neuroadaptations and contribute to the initial conditioning and motivational effects elicited by nicotine.
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Epigenetic Mechanisms Associated with Addiction-related Behavioural Effects of Nicotine and/or Cocaine: Implication of the Endocannabinoid System
Hayase, Tamaki (October 2017)
The addictive use of nicotine (NC) and cocaine (COC) continues to be a major public health problem, and their combined use has been reported, particularly during adolescence. In neural plasticity, commonly induced by NC and COC, as well as behavioural plasticity related to the use of these two drugs, the involvement of epigenetic mechanisms, in which the reversible regulation of gene expression occurs independently of the DNA sequence, has recently been reported. This article presents the addiction-related behavioural effects of NC and/or COC, based on the common behavioural/neural plasticity and combined use of NC/COC, and reviews the interacting role of the ECB system.
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Fatty Acid Amide Hydrolase (FAAH) Inactivation Confers Enhanced Sensitivity to Nicotine‐induced Dopamine Release in the Mouse Nucleus Accumbens
Francisco J. Pavon, Antonia Serrano, Nimish Sidhpura, Ilham Polis, David Stouffer, Fernando Rodriguez de Fonseca, Benjamin F. Cravatt, Rémi Martin‐Fardon, Loren H. Parsons (June 2017)
Nicotine exerts its rewarding effects by promoting an increase in dopamine (DA) release in the nucleus accumbens (NAc), and this process is influenced by the endocannabinoid system. Fatty acid amide hydrolase (FAAH) is the main enzyme responsible for the degradation of the endocannabinoid anandamide and other non‐cannabinoid N‐acylethanolamines. Previous research has reported that both genetic deletion and pharmacological inhibition of FAAH enhance nicotine‐induced conditioned place preference at low doses.
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The Endocannabinoid System as a Target for Addiction Treatment: Trials and Tribulations
Matthew E.Sloan, Joshua L.Gowin, Vijay A.Ramchandani, Yasmin L.Hurd, BernardLe Foll (May 2017)
Endocannabinoid signaling is involved in reward and addiction, which raises the possibility that drugs targeting this system could be used to treat substance use disorders. This review discusses findings from randomized controlled trials evaluating cannabinergic medications for addiction.
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Endocannabinoid Signaling in Reward and Addiction: From Homeostasis to Pathology
Sarah A. Laredo, William R. Marrs, Loren H. Parsons (May 2017)
The endogenous cannabinoid system is an important regulatory system involved in physiological homeostasis. Endocannabinoid signaling is known to modulate neural development, immune function, metabolism, synaptic plasticity, and emotional state. Accumulating evidence also implicates brain endocannabinoid signaling in the processing of natural and drug-induced reward states and dysregulated endocannabinoid signaling in the etiology of aberrant reward function and drug addiction.
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Cannabinoids and the Addictive Effects of Nicotine
L.V. Panlilio, S.R. Goldberg (2017)
Δ9-Tetrahydrocannabinol (THC) and nicotine are commonly used together in the form of cannabis and tobacco. Besides sharing similar routes of administration, these drugs affect reward-related brain circuits that partially overlap and interact. This interaction could be responsible for promoting addiction in co-users, but it might also provide new avenues for the treatment of addiction.
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The Endocannabinoid system: A New Molecular Target for the Treatment of Tobacco Addiction
Maria Scherma, Paola Fadda, Bernard Le Foll, Benoit Forget, Walter Fratta, Steven R. Goldberg, and Gianluigi Tanda (November 2008)
This review will focus on the recently published literature about the role of the endocannabinoid system in nicotine addiction and on the endocannabinoid system as a novel molecular target for the discovery of medications for tobacco dependence.
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Compliment or Substitute? Impact of Marijuana Legalization on Alcohol Consumption
Edvinas Rupkus (May 2019)
This paper uses a state-level alcohol sales dataset to analyze how marijuana legalization affects alcohol consumption. I employ a difference-in-differences model to investigate the relationship between alcohol and marijuana in the short-term and long-term. In addition, marijuana legalization effects are estimated for different alcohol types – beer, wine and spirits. Overall, the results indicate a negative, yet insignificant relationship between the two narcotic drugs. There is not enough evidence to firmly conclude substitutability or complementarity of the two goods, therefore, leaving the debate unsolved.
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