Brandon Stephen Bentzley

• MD PhD
• Professor (Assistant) at Stanford University

Patients with opioid use disorders frequently discontinue opioid maintenance therapy (OMT) prematurely, reducing retention and possibly limiting the efficacy of OMT. The current study is a cross-sectional survey of patients (N=69) enrolled in buprenorphine maintenance therapy (BMT). We examined patient demographics, BMT characteristics (e.g., dose,...

The orexin/hypocretin system is involved in multiple cocaine addiction processes that involve drug-associated environmental cues, including cue-induced reinstatement of extinguished cocaine seeking and expression of conditioned place preference. However, the orexin system does not play a role in several behaviors that are less cue-dependent, such a...

Buprenorphine maintenance therapy (BMT) is increasingly the preferred opioid maintenance agent due to its reduced toxicity and availability in an office-based setting in the United States. Although BMT has been shown to be highly efficacious, it is often discontinued soon after initiation. No current systematic review has yet investigated providers...

Significance Cocaine addiction is a major public health problem with no current pharmacotherapy approved by the US Food and Drug Administration. To accelerate discovery of treatments, we developed an animal model based on economics. Economics allows mathematical alignment of animal and human behavior, permitting more confident predictions of effica...

Rationale: Behavioral-economic demand curve analysis offers several useful measures of drug self-administration. Although generation of demand curves previously required multiple days, recent within-session procedures allow curve construction from a single 110-min cocaine self-administration session, making behavioral-economic analyses available t...

Aim: We investigated the impact of repetitive transcranial magnetic stimulation (rTMS) for treatment-resistant depression on healthcare resource utilization as well as commercial and Medicare Fee-for-Service payer costs. Materials & methods: We conducted a retrospective observational analysis of claims data using Medicare Fee-for-Service datasets a...

The neuromodulators dopamine (DA) and serotonin (5-hydroxytryptamine; 5HT) powerfully regulate associative learning1, 2, 3, 4, 5, 6, 7–8. Similarities in the activity and connectivity of these neuromodulatory systems have inspired competing models of how DA and 5HT interact to drive the formation of new associations9, 10, 11, 12, 13–14. However, th...

Our objective was to evaluate an optimized SAINT continuation treatment paradigm for treatment resistant depression (TRD) patients who initially remitted with SAINT with the goal of maintaining remission. Throughout 12 months of personalized continuation therapy (PCT) as indicated by a proprietary algorithm, we found participants' average MADRS s...

The neuromodulators dopamine (DA) and serotonin (5-hydroxytryptamine; 5HT) are powerful regulators of associative learning. Similarities in the activity and connectivity of these neuromodulatory systems have inspired competing models of how DA and 5HT interact to drive the formation of new associations. However, these hypotheses have yet to be test...

Dopamine (DA) release in the ventral and dorsal striatum has been linked to reward processing and motivation, but there are longstanding controversies about whether DA release in these key target structures primarily reflects costs or benefits, and how these signals vary with motivation. Here we apply behavioral economic principles to generate dema...

Objective: Depression is the leading cause of disability worldwide, and half of patients with depression have treatment-resistant depression. Intermittent theta-burst stimulation (iTBS) is approved by the U.S. Food and Drug Administration for the treatment of treatment-resistant depression but is limited by suboptimal efficacy and a 6-week duratio...

The origins and neural bases of the current opioid addiction epidemic are unclear. Genetics plays a major role in addiction vulnerability, but cannot account for the recent exponential rise in opioid abuse, so environmental factors must contribute. Individuals with history of early life adversity (ELA) are disproportionately prone to opioid addicti...

Importance: In the US and the United Kingdom, cocaine use is the second leading cause of illicit drug overdose death. Psychosocial treatments for cocaine use disorder are limited, and no pharmacotherapy is approved for use in the US or Europe. Objective: To compare treatments for active cocaine use among adults. Data sources: PubMed and the Co...

Objectives Cocaine is the second most frequently used illicit drug worldwide (after cannabis), and cocaine use disorder (CUD) related deaths increased globally by 80% from 1990 to 2013. There is yet to be a regulatory-approved treatment. Emerging preclinical evidence indicates that deep brain stimulation (DBS) of the nucleus accumbens may be a ther...

The role dopamine plays in reward-related behaviors has been debated for decades. Heymann et al. (Heymann G, Jo YS, Reichard KL, McFarland N, Chavkin C, Palmiter RD, Soden ME, Zweifel LS. Neuron 105(5): 909-920, 2020) identify subpopulations of dopamine-producing neurons that separately mediate reward association and motivation. Their results help...

Background: In both the U.S. and U.K., after a period of decline, prevalence of cocaine use has been increasing since 2012 and is now the second leading cause of overdose death from an illicit drug. However, psychosocial treatments for cocaine use disorders are limited, and no pharmacotherapy is approved by regulatory bodies in the U.S. or Europe....

Background: The prevalence of eating disorders, including binge eating disorder, is significantly higher in women. These findings are mirrored by preclinical studies, which indicate that female rats have a higher preference for palatable food and show greater binge-like eating compared to male rats. Methods: Here, we describe a novel within-sess...

Aberrant social behavior is a core feature of many neuropsychiatric disorders, yet the study of complex social behavior in freely moving rodents is relatively infrequently incorporated into preclinical models. This likely contributes to limited translational impact. A major bottleneck for the adoption of socially complex, ethology-rich, preclinical...

Objective: New antidepressant treatments are needed that are effective, rapid acting, safe, and tolerable. Intermittent theta-burst stimulation (iTBS) is a noninvasive brain stimulation treatment that has been approved by the U.S. Food and Drug Administration for treatment-resistant depression. Recent methodological advances suggest that the curre...

Rationale Comorbid use of heroin and cocaine is highly prevalent among drug users and can greatly increase addiction risk. Nonetheless, little is known regarding how a multi-drug history impacts motivation and cue responsivity to individual drugs. Objective We used behavioral-economic procedures to examine motivation to maintain drug consumption a...

We recently reported that naltrexone blocks antidepressant effects of ketamine in humans, indicating that antidepressant effects of ketamine require opioid receptor activation. However, it is unknown if opioid receptors are also involved in ketamine’s antisuicidality effects. Here, in a secondary analysis of our recent clinical trial, we test wheth...

: Drug courts are specialty courts that offer treatment services as alternatives to incarceration for defendants struggling with problems related to substance use. These courts have become major access points in the United States for the treatment of substance use disorders, but drug court participants often have limited access to medications for a...

Background: Insomnia and other types of sleep disturbance are highly prevalent during withdrawal across many different types of substance use disorders (SUDs). It is largely unknown how sleep impacts SUD treatment outcomes, including treatment completion. Methods: A retrospective chart review was conducted to obtain information about sleep distu...

The origins and neural bases of the current opioid addiction epidemic are unclear. Genetics plays a major role in addiction vulnerability, but cannot account for the exponential recent rise in opioid abuse, so environmental factors must contribute. Individuals with history of early-life adversity (ELA) are disproportionately affected, yet whether E...

Lateral hypothalamus (LH) orexin neuron signaling has been implicated in the motivation to seek and take drugs of abuse. The number of LH orexin neurons has been shown to be upregulated with exposure to drugs of abuse. We sought to determine if the number of LH orexin neurons related to individual differences in motivation (demand) for cocaine in o...

Background: Major depressive disorder (MDD) is prevalent and debilitating, and development of improved treatments is limited in part by insufficient understanding of the mechanism of disease remission. In turn, efforts to elucidate mechanisms have been challenging due to disease heterogeneity and limited effectiveness of treatments, which require w...

To the Editor The Research Letter by Yoon and colleagues,¹ published in JAMA Psychiatry, addresses our group’s recent finding that ketamine’s antidepressant effect is opioid-receptor dependent.² Their Letter makes clear that a better understanding of ketamine’s abuse liability should be a high priority to the field, particularly given the recent US...

Background Current treatments for depression are limited by suboptimal efficacy, delayed response, and frequent side effects. Intermittent theta-burst stimulation (iTBS) is a non-invasive brain stimulation treatment that is FDA-approved for treatment-resistant depression (TRD). Recent methodological advancements suggest iTBS could be improved throu...

Background: Intermittent theta-burst stimulation (iTBS) is an FDA-approved treatment for treatment-resistant depression (TRD). Typical courses involve daily stimulation sessions for six weeks and average response rates are around 50%. Several studies have demonstrated the safety and potential enhanced efficacy of accelerated theta-burst stimulation...

Background: Intermittent theta-burst stimulation (iTBS) is an FDA-approved treatment for treatment-resistant depression (TRD). Typical courses involve daily stimulation sessions for six weeks and average response rates are around 50%. Several studies have demonstrated the safety and potential enhanced efficacy of accelerated theta-burst stimulation...

Background: There is a high incidence of depression and suicidal ideation in patients with alcohol use disorder (AUD) and depressive symptoms are a strong predictor of relapse. Six-weeks of daily intermittent theta-burst stimulation (iTBS) is FDA-approved for treatment-resistant depression (TRD). The six-week duration means it is not feasible to de...

Lateral hypothalamus (LH) orexin neuron signaling has been implicated in the motivation to seek and take drugs of abuse. The number of LH orexin neurons has been shown to vary with behavioral state and can be upregulated with exposure to drugs of abuse. We sought to determine if the number of LH orexin neurons related to individual differences in m...

Behavioral investigation of motivation and cue senstivity with single verus multi-drug history of heroin and cocaine consumption in rat self-administration models.

Ventral tegmental area (VTA) dopamine (DA) neurons perform diverse functions in motivation and cognition, but their precise roles in addiction-related behaviors are still debated. Here, we targeted VTA DA neurons for bidirectional chemogenetic modulation during specific tests of cocaine reinforcement, demand, and relapse-related behaviors in male r...

Opioid use disorders (OUDs) carry widespread public health implications in the USA. Surveys from 2016 suggest that 11.8 million Americans had misused opioids in the past year and 2.1 million met criteria for an OUD. These disorders can devastate patients’ lives. Consequences of OUDs include social stigmatization, family disruptions, financial insta...

Ventral tegmental area (VTA) dopamine (DA) neurons perform diverse functions in motivation and cognition, but their precise roles in addiction-related behaviors are still debated. Here, we targeted VTA DA neurons for bidirectional chemogenetic modulation during specific tests of cocaine reinforcement, demand, and relapse-related behaviors, querying...

Decision-making about the expected value of an experience or behavior can explain hearing health behaviors in older adults with hearing loss. Forty-four middle-aged to older adults (68.45 ± 7.73 years) performed a task in which they were asked to decide whether information from a surgeon or an administrative assistant would be important to their he...

Background: Evidence indicates that oxytocin, an endogenous peptide well known for its role in social behaviors, childbirth, and lactation, is a promising addiction pharmacotherapy. We employed a within-session behavioral-economic (BE) procedure in rats to examine oxytocin as a pharmacotherapy for methamphetamine (meth) addiction. The BE paradigm...

Rationale: Contemporary animal models of cocaine addiction focus on increasing the amount of drug consumption to produce addiction-like behavior. However, another critical factor is the temporal pattern of consumption, which in humans is characterized by intermittency, both within and between bouts of use. Objective: To model this, we combined p...

Background: Epidural prefrontal cortical stimulation (EpCS) represents a novel therapeutic approach with many unique benefits that can be used for treatment-resistant depression (TRD). Objective: To examine the long-term safety and efficacy of EpCS of the frontopolar cortex (FPC) and dorsolateral prefrontal cortex (DLPFC) for treatment of TRD....

Objectives: Electroconvulsive therapy (ECT) has demonstrated efficacy in treating core symptoms of Parkinson's disease (PD); however, widespread use of ECT in PD has been limited due to concern over cognitive burden. We investigated the use of a newer ECT technology known to have fewer cognitive side effects (right unilateral [RUL] ultra-brief pul...

Preclinical evidence indicates that inactivation of subthalamic nucleus (STN) may be effective for treating cocaine addiction, and therapies that target STN, e.g. deep brain stimulation, are available indicating that this may have clinical promise. Here, we assessed the therapeutic potential of STN inactivation using a translationally relevant econ...

Orexin-1 receptors (Ox1Rs) have been implicated in the motivation for drugs of abuse. Here, we utilized a within-session behavioral-economics threshold procedure to screen for individual differences in economic demand for the ultra-short-acting opioid remifentanil and to test whether antagonism of Ox1Rs reduces remifentanil demand. The behavioral-e...

Background Delay discounting (DD) is a measure of impulsivity that quantifies preference for a small reward delivered immediately over a large reward delivered after a delay. It has been hypothesized that impulsivity is an endophenotype associated with increased risk for development of alcohol use disorders (AUDs); however, a causal role of impulsi...

All living organisms depend on homeostasis, the complex set of interacting metabolic chemical reactions for maintaining life and well‐being. This is no less true for psychiatric well‐being than for physical well‐being. Indeed, a focus on homeostasis forces us to see how inextricably linked mental and physical well‐being are. This paper focuses on t...

Dusty plasmas were studied in an experiment designed to investigate the impact of gravity on particle (80 micron) dynamics. The experiment used a CCD camera and thin laser-sheet to image silica dust clouds that were exposed to UV light (100W, 365nm) within an argon DC glow discharge plasma (300mT, 0.65ma) aboard NASA's ``Weightless Wonder.'' The We...