Mixed amphetamine salts-extended release (MAS-ER) as a behavioral treatment augmentation strategy for cocaine use disorder: A randomized clinical trial.

Psychosocial interventions remain the primary strategy for addressing cocaine use disorder (CUD), although many individuals do not benefit from these approaches. Amphetamine-based interventions have shown significant promise and may improve outcomes among individuals continuing to use cocaine in the context of behavioral interventions. One hundred forty-five adults (122 males) who used cocaine a minimum of 4 days in the prior month and met the criteria for a CUD enrolled in a two-stage intervention. All participants received a computer-delivered skills intervention and contingency management for reinforcing abstinence for a 1-month period. Participants demonstrating less than 3 weeks of abstinence in the first month were randomized to receive mixed amphetamine salts-extended release (MAS-ER) or placebo (80 mg/day) for 10 weeks under double-blind conditions. All participants continued with the behavioral intervention. The primary outcome was the proportion of individuals who achieved 3 consecutive weeks of abstinence as measured by urine toxicology confirmed self-report at the study end. The proportion of participants demonstrating 3 consecutive weeks of abstinence at study end did not differ between the medication groups: MAS-ER = 15.6% (7/45) and placebo = 12.2% (5/41). Participants who received MAS-ER reported greater reductions in the magnitude of wanting cocaine, although no group differences were noted in either the perceived improvement or the frequency of wanting cocaine. Retention rates were greater for both medication groups compared to behavioral responders. Overall, augmenting a behavioral intervention with MAS-ER did not significantly increase the abstinence rate among individuals continuing to use cocaine following a month of behavioral therapy alone. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Environmental cues can indirectly acquire cocaine-eliciting changes in Heart Rate: A pilot study of derived relational responding, the transfer of function among cocaine users.

Identifying the processes by which environmental stimuli can come to influence drug use is important for developing more efficacious interventions. This study investigated derived relational responding and the transfer of differential conditioned effects of environmental stimuli paired with "smoked" cocaine in accordance with the relations of symmetry, transitivity, and equivalence using Heart Rate as the measure of conditioning among 12 adults with significant histories of cocaine use. Match-to-sample (MTS) procedures were used to test for emergent relations among two four-member stimulus groupings. One member of a group was then paired with 25-mg of smoked cocaine and one member of the other group was paired with 0-mg of smoked cocaine. 10 participants completed the MTS protocol: 4 participants demonstrated two four-member equivalence classes, 3 participants demonstrated two three-member equivalence classes and 2 participants demonstrated symmetry only. One participant demonstrated no derived relations. Differential respondent elicited changes in HR was demonstrated in the presence of stimuli paired with smoked cocaine among 4 of the 6 participants completing the conditioning phase; all 4 of the participants demonstrated a bi-directional transfer of these functions in accordance with symmetry. Transfer was not reliably demonstrated in accordance with transitive or equivalence relations. The results suggest that drug respondent elicitation in the context of drug use may be a function of both direct conditioning and relational processes. These findings have implications for studying and understanding the processes by which stimuli in the natural ecology can set the occasion for cocaine use and developing cocaine use disorder.

Pilot randomized placebo-controlled clinical trial of high-dose gabapentin for alcohol use disorder.

BACKGROUND: Despite advances in the development of pharmacotherapy for alcohol use disorder (AUD), there remains a need for medications that can be administered to actively drinking outpatients to promote a reduction in harmful alcohol consumption. The primary aim of this pilot study was to determine whether high-dose gabapentin (3600 mg/daily) is more effective than placebo in reducing harmful alcohol consumption in outpatients with AUD. METHODS: Forty patients (27 men) who met DSM-IV-TR criteria for alcohol dependence and reporting at least 4 heavy drinking days (HDD) per week were recruited at a single site. Participants were actively drinking at study entry and received double-blind gabapentin (3600 mg/day; n = 19) or placebo (n = 20) for 8 weeks. Study medication was titrated over 5 days and administered in three divided doses (1200 mg three times per day). The proportion of HDD (primary outcome) and percent days abstinent (PDA; secondary outcome) were analyzed using generalized longitudinal mixed models with the predictors being study arm, week, study arm by week interaction, and corresponding baseline drinking measure. RESULTS: There was a significant interaction between study arm and week for the proportion of HDD per week, F (7, 215) = 3.33, p = 0.002 . There was also a significant interaction between study arm and week for PDA per week, F (7, 215) = 3.11, p = 0.004. The overall retention rate was 67.5% with no significant difference in time-to-dropout between treatment groups. There were no serious adverse events. No participants were removed from the trial due to the development of moderate-to-severe alcohol withdrawal (CIWA-Ar ≥ 13). CONCLUSIONS: Gabapentin treatment rapidly titrated to a dosage of 3600 mg/day is associated with a reduction in the proportion of HDD per week and an increase in PDA per week in actively drinking outpatients with AUD. High-dose gabapentin is potentially a feasible approach to treating AUD and deserving of further study.

Quetiapine treatment for cannabis use disorder.

BACKROUND: Pharmacotherapy for cannabis use disorder (CUD) is an important unmet public health need. METHODS: In a 12-week randomized double-blind placebo-controlled trial, the efficacy of quetiapine (300 mg nightly) for the treatment of CUD was tested in 130 outpatients. Weekly cannabis use was categorized into three groups: heavy use (5-7 days), moderate use (2-4 days) and light use (0-1 days). RESULTS: At baseline both groups were considered heavy users (using days per week: median = 7.0; interquartile range (IQR): 6.5-7.0; daily dollar value: median = $121.4; IQR: 73.8-206.3). The week-by-treatment interaction was marginally significant (χ2(2) = 5.56, P = .06). With each week, the odds of moderate compared to heavy use significantly increased in the quetiapine group (OR=1.17, P < .0001), but not significantly in the placebo group (OR=1.05, P = .16). The odds of light versus heavy use did not significantly differ over time (P = .12). Treatment was also associated with reduced cannabis withdrawal symptoms by 10.4% each week (95% CI: 8.9-11.8). No serious adverse events occurred during the study and no evidence of development of a movement disorder was detected. Adverse effects were not significantly different between the quetiapine and placebo treatment arms. CONCLUSIONS: The use of quetiapine to treat CUD was associated with an increased likelihood of heavy frequency use transitioning to moderate use, but not light use. The clinical significance of reductions in cannabis use, short of abstinence warrants further study.

An adaptive clinical trial design for cocaine use disorder: Extended-release amphetamine salts for early behavioral intervention non-responders.

BACKGROUND/AIMS: Cocaine use disorder (CUD) persists as a major public health problem in the United States. Response to evidence-based behavioral treatment has been shown to be predicted by dopaminergic dysfunction. Amphetamine formulations modulate dopaminergic systems and are one of the few agents with positive clinical findings but are associated with unique risks. We aimed to find a model for determining the most appropriate patients for treatment with mixed amphetamine salts-extended-release (MAS-ER) for CUD using an adaptive trial design. METHODS: We are enrolling treatment-seeking adults ages 18-60 years. All eligible participants receive bi-weekly individual counseling augmented with a computer-based intervention based on the community reinforcement approach with contingency management (CRA + CM) for 4 weeks. Participants who fail to achieve abstinence are additionally randomly assigned to 10 weeks of either MAS-ER, titrated up to 80 mg daily, or placebo. All participants complete a follow-up assessment after 12 weeks. RESULTS: Frequency and amount of cocaine use, cravings, retention, and quality of life will be compared between groups. The primary outcome will be having at least 3 weeks of urine toxicology-confirmed self-reported abstinence. Analyses will also be conducted to identify variables that may help identify who is more or less likely respond to the behavioral intervention during the first 4-weeks of treatment. CONCLUSIONS: This trial more closely mimics a personalized medicine approach that is often used in clinical practice. It will help us understand who may be appropriate for psychostimulant therapy as an enhancement to evidence-based behavioral interventions, while limiting exposure to those who would respond to a psychosocial intervention alone. ClinicalTrials.gov Identifier: NCT01986075.

Evidence for Dopamine Abnormalities in the Substantia Nigra in Cocaine Addiction Revealed by Neuromelanin-Sensitive MRI.

OBJECTIVE: Recent evidence supports the use of neuromelanin-sensitive MRI (NM-MRI) as a novel tool to investigate dopamine function in the human brain. The authors investigated the NM-MRI signal in individuals with cocaine use disorder, compared with age- and sex-matched control subjects, based on previous imaging studies showing that this disorder is associated with blunted presynaptic striatal dopamine. METHODS: NM-MRI and T1-weighted images were acquired from 20 participants with cocaine use disorder and 35 control subjects. Diagnostic group effects in NM-MRI signal were determined using a voxelwise analysis within the substantia nigra. A subset of 20 cocaine users and 17 control subjects also underwent functional MRI imaging using the monetary incentive delay task, in order to investigate whether NM-MRI signal was associated with alterations in reward processing. RESULTS: Compared with control subjects, cocaine users showed significantly increased NM-MRI signal in ventrolateral regions of the substantia nigra (area under the receiver operating characteristic curve=0.83). Exploratory analyses did not find a significant correlation of NM-MRI signal to activation of the ventral striatum during anticipation of monetary reward. CONCLUSIONS: Given that previous imaging studies show decreased dopamine signaling in the striatum, the finding of increased NM-MRI signal in the substantia nigra provides additional insight into the pathophysiology of cocaine use disorder. One interpretation is that cocaine use disorder is associated with a redistribution of dopamine between cytosolic and vesicular pools, leading to increased accumulation of neuromelanin. The study findings thus suggest that NM-MRI can serve as a practical imaging tool for interrogating the dopamine system in addiction.

Use of scaled dinosaur bones in taphonomic water flume experiments.

Laboratory water flumes are artificial troughs of moving water widely used in hydraulic studies of fluvial systems to investigate real-world problems at smaller, more manageable scales. Water flumes have also been used to understand bone transportation sorting and bone orientation found in the fossil record using actual bones. To date, these studies have not involved scaled bones. A 1/12 scale model of a 21.8-m long skeleton of Apatosaurus, a long-necked sauropod dinosaur from the Late Jurassic, was used to explore three problems at Dinosaur National Monument (USA) that cannot be explained by tradition bone flume studies: (1) why there is an abrupt bend in articulated vertebrae, (2) why articulated dorsals are inverted relative to the pelvis, and (3) how bone jams form. The flume experiments established that (1) bed friction with the wing-like transverse processes of vertebrae resists the force of the water flow, whereas those vertebrae lacking the processes are free to pivot in the flow; (2) elevation of the dorsal vertebrae by the transverse processes subjects the vertebrae to the energy of the flow stream, which causes the vertebrae to flip. Computation fluid dynamics (CFD) software shows this flip was due to differential pressure on the upstream and downstream sides. (3) The formation and growth of bone clusters or jams (analogous to log jams in rivers) occur as transported bones pile against an initial obstruction and jammed bones themselves become obstacles. These preliminary studies show that scale models can provide valuable insights into certain taphonomic problems that cannot be obtained by traditional bone flume studies.

Building on shared experiences: The evaluation of a phone-based parent-to-parent support program for helping parents with their child's substance misuse.

AIMS: To evaluate the feasibility and acceptability of a phone-based parent-to-parent support program, in which parents who have had children with substance use problems provided support and guidance to other parents seeking help about their child's substance misuse. METHOD: 228 parents completed a 2.5-day coach workshop and 6-months of ongoing training and support in the Invitation to Change Approach (ITC), a program blending evidence-based strategies for addressing substance use disorders. Trained parent coaches provided support and guidance to 278 parents for up to 8 weeks. We evaluated the coach trainees' satisfaction with the training program and pre-post differences in self-care and the use of communication and behavior management strategies among parents who called the helpline. RESULTS: The coach training program was rated as very satisfying, useful, and coaches would recommend the training to other parents. Among parents enrolled in the coaching program, a significantly greater proportion reported improvements on a majority of the survey items (e.g. a decrease in depression and better communication with child). CONCLUSIONS: Remote parent-to-parent coaching appears promising for providing emotional and evidence-based informational support to family members parenting a child with substance use problems.

Extended release mixed amphetamine salts and topiramate for cocaine dependence: A randomized clinical replication trial with frequent users.

BACKGROUND: Cocaine use disorder (CUD) remains a substantial public health problem with no clearly effective pharmacotherapy available. In a prior trial, combined amphetamine and topiramate treatment significantly reduced cocaine use among individuals demonstrating the most frequent use at baseline. This trial targeted such frequent users. METHODS: A double-blind, randomized placebo-controlled trial, testing the combination of mixed amphetamine salts extended-release (MAS-ER) and topiramate or placebo over a 12-week medication phase was conducted. The two-site outpatient trial included 127 adults (96 males) with CUD using at least 9 days in the prior month. MAS-ER was titrated to a maximum dose of 60 mg/day and topiramate to a maximum dose of 100 mg twice/day. The primary outcome was the proportion of individuals who achieved three consecutive abstinent weeks at the end of the study (EOS) as measured by urine toxicology and self-report. RESULTS: The proportion of participants achieving three abstinent weeks at the EOS was significantly (P = .03) larger in the treatment (14.1%) compared to the placebo group (0.0%), while controlling for baseline cocaine use, sex, current alcohol use disorder, and site. Of note, due to conservative cardiac safety-parameters a considerable number of individuals in the treatment group were discontinued from study medication (20.3%). CONCLUSIONS: While these findings provide further evidence that the combination of MAS-ER and topiramate is efficacious in promoting abstinence in CUD adults with frequent use it remains possible that the combination treatment is no more effective than either treatment alone. Despite this, the study provides a valuable "proof of concept."

A Single Ketamine Infusion Combined With Mindfulness-Based Behavioral Modification to Treat Cocaine Dependence: A Randomized Clinical Trial.

OBJECTIVE: Research has suggested that subanesthetic doses of ketamine may work to improve cocaine-related vulnerabilities and facilitate efforts at behavioral modification. The purpose of this trial was to test whether a single ketamine infusion improved treatment outcomes in cocaine-dependent adults engaged in mindfulness-based relapse prevention. METHODS: Fifty-five cocaine-dependent individuals were randomly assigned to receive a 40-minute intravenous infusion of ketamine (0.5 mg/kg) or midazolam (the control condition) during a 5-day inpatient stay, during which they also initiated a 5-week course of mindfulness-based relapse prevention. Cocaine use was assessed through self-report and urine toxicology. The primary outcomes were end-of-study abstinence and time to relapse (defined as first use or dropout). RESULTS: Overall, 48.2% of individuals in the ketamine group maintained abstinence over the last 2 weeks of the trial, compared with 10.7% in the midazolam group (intent-to-treat analysis). The ketamine group was 53% less likely (hazard ratio=0.47; 95% CI=0.24, 0.92) to relapse (dropout or use cocaine) compared with the midazolam group, and craving scores were 58.1% lower in the ketamine group throughout the trial (95% CI=18.6, 78.6); both differences were statistically significant. Infusions were well tolerated, and no participants were removed from the study as a result of adverse events. CONCLUSIONS: A single ketamine infusion improved a range of important treatment outcomes in cocaine-dependent adults engaged in mindfulness-based behavioral modification, including promoting abstinence, diminishing craving, and reducing risk of relapse. Further research is needed to replicate these promising results in a larger sample.

A Randomized Trial Comparing Extended-Release Injectable Suspension and Oral Naltrexone, Both Combined With Behavioral Therapy, for the Treatment of Opioid Use Disorder.

OBJECTIVE: The oral formulation of the opioid antagonist naltrexone has shown limited effectiveness for treatment of opioid use disorder due to poor adherence. Long-acting injection naltrexone (XR-naltrexone), administered monthly, circumvents the need for daily pill taking, potentially improving adherence, and has been shown to be superior to placebo in reducing opioid use over 6 months of treatment. This open-label trial compared the outcomes of patients with opioid use disorder treated with XR-naltrexone or oral naltrexone in combination with behavioral therapy. METHOD: Sixty opioid-dependent adults completed inpatient opioid withdrawal and were transitioned to oral naltrexone. They were stratified by severity of opioid use (six or fewer bags versus more than six bags of heroin per day) and randomly assigned (1:1) to continue treatment with oral naltrexone (N=32) or XR-naltrexone (N=28) for 24 weeks. The first dose of XR-naltrexone (380 mg) was administered prior to discharge, with monthly doses thereafter, and oral naltrexone was given in a 50-mg daily dose. All participants received weekly behavioral therapy to support treatment and adherence to naltrexone. RESULTS: A Cox proportional hazards model adjusting for race, gender, route of use, and baseline opioid use severity indicated that significantly more patients were retained in treatment for 6 months in the XR-naltrexone group (16 of 28 patients, 57.1%) than in the oral naltrexone group (nine of 32 patients, 28.1%) (hazard ratio=2.18, 95% CI=1.07, 4.43). CONCLUSIONS: Patients receiving XR-naltrexone had twice the rate of treatment retention at 6 months compared with those taking oral naltrexone. These results support the use of XR-naltrexone combined with behavioral therapy as an effective treatment for patients seeking opioid withdrawal and nonagonist treatment for preventing relapse to opioid use disorder.

Making risky decisions to take drug: Effects of cocaine abstinence in cocaine users.

Risky decision-making is characteristic of drug users, but little is known about the effects of circumstances, such as abstinence, on risky choice behavior in human drug users. We hypothesized that cocaine users would make more risky choices for cocaine (defined as taking a chance to receive a large number of cocaine doses as opposed to choosing to receive a fixed amount of cocaine) after 3 or 7 days of cocaine abstinence, compared to 1 day of cocaine abstinence. Six male nontreatment-seeking current cocaine smokers were enrolled in a 21-day inpatient within-subject study. Participants repeatedly smoked six 25 mg doses of cocaine during a training session and were instructed that they would be making decisions about smoking this dose throughout the study. After 1, 3 and 7 days of cocaine abstinence, participants completed a computerized task in which they repeatedly decided between receiving a guaranteed number of cocaine doses (between 1 and 5; fixed option) or receiving a chance (0.13 to 0.75) to smoke a larger number of cocaine doses (probabilistic option). After completing the computerized task, one of the participants' choices was randomly implemented and they smoked either the fixed number of cocaine doses or had the specified chance to smoke the greater number of doses. Contrary to our hypothesis, 5 of the 6 participants made fewer risky choices after 3 and 7 days of cocaine abstinence compared to one day of abstinence suggesting greater risk-aversion. Thus, even during cocaine abstinence cocaine users make rational decisions related to their drug use.

The Impact of Dust/Gas Ratios on Chromospheric Activity in Red Giant and Supergiant Stars.

Stencel et al. (1986) analyzed IUE spectra of a modest set of cool stars and found that they continue to produce chromospheres even in the presence of high dust levels in their outer atmospheres. This reversed the previous results of Jennings (1973) and Jennings & Dyck (1972). We describe an on-going extension of these studies to a sample of stars representing a broader range in dust/gas ratios, using archival IUE and archival and new HST data on both RGB and AGB stars. Surface fluxes in emission lines will be analyzed to assess the chromospheric activity and obscuration by dust in each star, as those fluxes will follow a different pattern for reduced activity (temperature/density dependent) vs. dust obscuration (wavelength dependent). Wind characteristics will be measured by modeling of wind-reversed chromospheric emission lines.

Perinate and eggs of a giant caenagnathid dinosaur from the Late Cretaceous of central China.

The abundance of dinosaur eggs in Upper Cretaceous strata of Henan Province, China led to the collection and export of countless such fossils. One of these specimens, recently repatriated to China, is a partial clutch of large dinosaur eggs (Macroelongatoolithus) with a closely associated small theropod skeleton. Here we identify the specimen as an embryo and eggs of a new, large caenagnathid oviraptorosaur, Beibeilong sinensis. This specimen is the first known association between skeletal remains and eggs of caenagnathids. Caenagnathids and oviraptorids share similarities in their eggs and clutches, although the eggs of Beibeilong are significantly larger than those of oviraptorids and indicate an adult body size comparable to a gigantic caenagnathid. An abundance of Macroelongatoolithus eggs reported from Asia and North America contrasts with the dearth of giant caenagnathid skeletal remains. Regardless, the large caenagnathid-Macroelongatoolithus association revealed here suggests these dinosaurs were relatively common during the early Late Cretaceous.

Long-Acting Injectable Naltrexone Induction: A Randomized Trial of Outpatient Opioid Detoxification With Naltrexone Versus Buprenorphine.

OBJECTIVE: At present there is no established optimal approach for transitioning opioid-dependent adults to extended-release injection naltrexone (XR-naltrexone) while preventing relapse. The authors conducted a trial examining the efficacy of two methods of outpatient opioid detoxification for induction to XR-naltrexone. METHOD: Participants were 150 opioid-dependent adults randomly assigned 2:1 to one of two outpatient detoxification regimens, naltrexone-assisted detoxification or buprenorphine-assisted detoxification, followed by an injection of XR-naltrexone. Naltrexone-assisted detoxification lasted 7 days and included a single day of buprenorphine followed by ascending doses of oral naltrexone along with clonidine and other adjunctive medications. Buprenorphine-assisted detoxification included a 7-day buprenorphine taper followed by a week-long delay before administration of XR-naltrexone, consistent with official prescribing information for XR-naltrexone. Participants from both groups received behavioral therapy focused on medication adherence and a second dose of XR-naltrexone. RESULTS: Compared with participants in the buprenorphine-assisted detoxification condition, participants assigned to naltrexone-assisted detoxification were significantly more likely to be successfully inducted to XR-naltrexone (56.1% compared with 32.7%) and to receive the second injection at week 5 (50.0% compared with 26.9%). Both models adjusted for primary type of opioid use, route of opioid administration, and morphine equivalents at baseline. CONCLUSIONS: These results demonstrate the safety, efficacy, and tolerability of low-dose naltrexone, in conjunction with single-day buprenorphine dosing and adjunctive nonopioid medications, for initiating adults with opioid dependence to XR-naltrexone. This strategy offers a promising alternative to the high rates of attrition and relapse currently observed with agonist tapers in both inpatient and outpatient settings.

Derived relations moderate the association between changes in the strength of commitment language and cocaine treatment response.

The psycholinguistic analysis of client-counselor interactions indicates that how individuals talk about their substance use is associated with treatment outcome. However, the processes by which client speech influences out-of-session behaviors have not been clearly delineated. This study investigated the relationships between deriving relations-a key behavioral process by which language and cognition may come to influence behavior, shifts in the strength of client talk in favor of change, and treatment outcome among 75 cocaine-dependent participants (23% Female). Participants were trained to relate cocaine words, nonsense syllables, and negative-consequence words and were then assessed for a derived relation of equivalence before starting treatment. The DARN-C coding system was used to quantify the strength of participant speech during an early cognitive behavior therapy counseling session. Cocaine use during treatment was the outcome of interest. The analyses (a) characterized the process of deriving relations among individuals seeking help for their misuse of cocaine, (b) tested the relationships between shifts in the strength of participants' speech in favor of change and treatment outcome, and (c) tested if deriving equivalence relations moderated the relationship between shifts in the strength of in-session speech and treatment response. Results indicated that a minority of participants derived equivalence relations, however increases in the strength of commitment language predicted less cocaine use during treatment only among those who did. The findings suggest deriving relations may be an important process by which changes in the strength of commitment language comes to influence substance use.

Pathological pitting in ankylosaur (Dinosauria) osteoderms.

Large ulcerative pits on the external surface of ankylosaur (Dinosauria) osteoderms have been recognized for many years. They have been ascribed without supporting evidence to damage by predator teeth or to disease. The discovery of numerous examples of pitted osteoderms in a monospecific ankylosaur (Gastonia n.sp.) bone bed in eastern Utah (USA) provided a unique opportunity to study these pits in greater detail. The pits typically are characterized by smooth-walled depressions that disrupt the bone surface, with 43% focal lesions and 57% multifocal. Because ankylosaur osteoderms are analogous to crocodile osteoderms, the possible etiology of the pits was sought among today's crocodile dermatoses. A modified version of the Istanbul Protocol was used to indicate the degree of certainty for the possible causes. This technique in context of the limited range of response to infection of reptile bone, allows us to narrow the possible causes of pit formation to two. One is ulceration by bacterial or mycological dermatosis; the other is through pressure erosion of the bone surface (cortex) by granuloma formation in the thin skin or at the skin-osteoderm interface. Unfortunately, the biopsies that are critical for differential diagnosis of diseases in modern reptiles cannot be performed on the ankylosaur osteoderms. Therefore, a single definitive etiology for pits in ankylosaurs cannot be identified.

Dronabinol and lofexidine for cannabis use disorder: A randomized, double-blind, placebo-controlled trial.

BACKGROUND: Cannabis use disorder is associated with substantial morbidity and, after alcohol, is the most common drug bringing adolescents and adults into treatment. At present, there are no FDA-approved medications for cannabis use disorder. Combined pharmacologic interventions might be particularly useful in mitigating withdrawal symptoms and promoting abstinence. OBJECTIVE: The purpose of this study was to evaluate the safety and efficacy of dronabinol, a synthetic form of delta-9-tetrahydrocannabinol, a naturally occurring pharmacologically active component of marijuana, and lofexidine, an alpha-2 agonist, in treating cannabis dependence. METHODS: One hundred fifty six cannabis-dependent adults were enrolled and following a 1-week placebo lead-in phase 122 were randomized in a double-blind, placebo-controlled, 11-week trial. Participants were randomized to receive dronabinol 20mg three times a day and lofexidine 0.6 mg three times a day or placebo. Medications were maintained until the end of week eight, were then tapered over two weeks and patients were monitored off medications during the last study week. All participants received weekly motivational enhancement and relapse prevention therapy. Marijuana use was assessed using the timeline follow-back method. RESULTS: There was no significant difference between treatment groups in the proportion of participants who achieved 3 weeks of abstinence during the maintenance phase of the trial (27.9% for the medication group and 29.5% for the placebo group), although both groups showed a reduction over time. CONCLUSIONS: Based on this treatment study, the combined intervention did not show promise as a treatment for cannabis use disorder.

Cranial osteology of the ankylosaurian dinosaur formerly known as Minmi sp. (Ornithischia: Thyreophora) from the Lower Cretaceous Allaru Mudstone of Richmond, Queensland, Australia.

Minmi is the only known genus of ankylosaurian dinosaur from Australia. Seven specimens are known, all from the Lower Cretaceous of Queensland. Only two of these have been described in any detail: the holotype specimen Minmi paravertebra from the Bungil Formation near Roma, and a near complete skeleton from the Allaru Mudstone on Marathon Station near Richmond, preliminarily referred to a possible new species of Minmi. The Marathon specimen represents one of the world's most complete ankylosaurian skeletons and the best-preserved dinosaurian fossil from eastern Gondwana. Moreover, among ankylosaurians, its skull is one of only a few in which the majority of sutures have not been obliterated by dermal ossifications or surface remodelling. Recent preparation of the Marathon specimen has revealed new details of the palate and narial regions, permitting a comprehensive description and thus providing new insights cranial osteology of a basal ankylosaurian. The skull has also undergone computed tomography, digital segmentation and 3D computer visualisation enabling the reconstruction of its nasal cavity and endocranium. The airways of the Marathon specimen are more complicated than non-ankylosaurian dinosaurs but less so than derived ankylosaurians. The cranial (brain) endocast is superficially similar to those of other ankylosaurians but is strongly divergent in many important respects. The inner ear is extremely large and unlike that of any dinosaur yet known. Based on a high number of diagnostic differences between the skull of the Marathon specimen and other ankylosaurians, we consider it prudent to assign this specimen to a new genus and species of ankylosaurian. Kunbarrasaurus ieversi gen. et sp. nov. represents the second genus of ankylosaurian from Australia and is characterised by an unusual melange of both primitive and derived characters, shedding new light on the evolution of the ankylosaurian skull.

The effects of dronabinol during detoxification and the initiation of treatment with extended release naltrexone.

BACKGROUND: Evidence suggests that the cannabinoid system is involved in the maintenance of opioid dependence. We examined whether dronabinol, a cannabinoid receptor type 1 partial agonist, reduces opioid withdrawal and increases retention in treatment with extended release naltrexone (XR-naltrexone). METHODS: Opioid dependent participants were randomized to receive dronabinol 30mg/d (n=40) or placebo (n=20), under double-blind conditions, while they underwent inpatient detoxification and naltrexone induction. Before discharge all participants received an injection of XR-naltrexone, with an additional dose given four weeks later. Dronabinol or placebo was given while inpatient and for 5 weeks afterwards. The primary outcomes were the severity of opioid withdrawal, measured with the Subjective Opioid Withdrawal Scale, and retention in treatment at the end of the inpatient phase and at the end of the 8-week trial. RESULTS: The severity of opioid withdrawal during inpatient phase was lower in the dronabinol group relative to placebo group (p=0.006). Rates of successful induction onto XR-naltrexone (dronabinol 66%, placebo 55%) and completion of treatment (dronabinol 35%, placebo 35%) were not significantly different. Post hoc analysis showed that the 32% of participants who smoked marijuana regularly during the outpatient phase had significantly lower ratings of insomnia and anxiety and were more likely to complete the 8-week trial. CONCLUSION: Dronabinol reduced the severity of opiate withdrawal during acute detoxification but had no effect on rates of XR-naltrexone treatment induction and retention. Participants who elected to smoke marijuana during the trial were more likely to complete treatment regardless of treatment group assignment.