Summary:Background: Acetone, one of the principal ketone bodies elevated during treatment with the ketogenic diet, exhibits anticonvulsant properties that may contribute to the seizure protection conferred by the diet. The anticonvulsant mechanism of acetone is unknown, but it is metabolized to several bioactive substances that could play a role.Methods: Acetone and its major metabolites-acetol, 1,2-propanediol, methylglyoxal, and pyruvic acid-were assessed for anticonvulsant activity in two mouse seizure models. Various doses of the substances administered intraperitoneally were characterized for their ability to elevate the threshold for clonic seizures induced by intravenous infusion of pentylenetetrazol (PTZ) and for protection against tonic seizures induced by subcutaneous bolus administration of 4-aminopyridine (4-AP). The inverted-screen test was used to assess acute neurological toxicity.Results: Acetone (1-32 mmol/kg, i.p.), in a dose-dependent fashion, elevated the PTZ threshold and conferred protection against 4-AP seizures (ED 50 , 26.3 mmol/kg). Effective doses of acetone (10-32 mmol/kg) did not cause motor impairment in the inverted-screen test (TD 50 , 45.7 mmol/kg). In doses 10-fold greater than the minimally effective dose of acetone (3.2 mmol/kg), the metabolites acetol, 1,2-propanediol, and pyruvic acid were inactive in the PTZ model. At higher doses that produced motor impairment, acetol and 1,2-propanediol (but not pyruvic acid) did elevate the PTZ threshold. Methylglyoxal had both proconvulsant and anticonvulsant actions, and had substantial toxicity, producing respiratory distress, motor impairment, and death. None of the acetone metabolites protected against 4-AP seizures.Conclusions: This study confirms the broad-spectrum anticonvulsant properties of acetone and indicates that the seizure protection conferred is unlikely to result from its major metabolic products.

BACKGROUND Psychiatric comorbidity can adversely affect opioid dependence treatment outcomes. While the prevalence of psychiatric comorbidity among patients seeking methadone maintenance treatment has been documented, the extent to which these findings extend to patients seeking primary care office-based buprenorphine/naloxone treatment is unclear. AIMS To determine the prevalence of mood and substance use disorders among patients seeking primary care office-based buprenorphine/naloxone treatment, via cross sectional survey. METHODS 237 consecutive patients seeking primary care office-based buprenorphine/naloxone treatment were evaluated using modules from the Structured Clinical Interview for DSM-IV Axis I Disorders (SCID-I). Current (past 30 days) and past diagnoses were catalogued separately. RESULTS Patients ranged in age from 18 to 62 years old (M = 33.9, SD = 9.9); 173 (73%) were men; 197 (83%) were white. Major depression was the most prevalent mood disorder (19% current, 24% past). A minority of patients met criteria for current dysthymia (6%), past mania (1%), or past hypomania (2%). While 37 patients (16%) met criteria for current abuse of or dependence on at least one non-opioid substance (7% cocaine, 4% alcohol, 4% marijuana, 2% sedatives, 0.4% stimulants, 0.4% polydrug), 168 patients (70%) percent met criteria for past abuse of or dependence on at least one non-opioid substance (43% alcohol, 38% marijuana, 30% cocaine, 9% sedatives, 8% hallucinogens, 4% stimulants, 1% polydrug, and 0.4% other substances). CONCLUSION Mood and substance use comorbidity is prevalent among patients seeking primary care office-based buprenorphine/naloxone treatment. The findings support the need for clinicians to assess and address these conditions.

Objectives Effective and safe pain management interventions in methadone maintenance treatment are needed. Methods We examined the feasibility (i.e., single session attendance) and acceptability (i.e., patient satisfaction, booster session attendance) of cognitive-behavioral therapy-informed groups for pain management: Coping with Pain, Relaxation Training, Group Singing, and Mindful Walking. Pre- and post-session measures were collected. Results 349 (out of a census of approximately 800) methadone-maintained patients attended at least one of the groups. Group satisfaction was high. Booster session attendance was numerically lower in Mindful Walking (15%) as compared to the other groups (at least 40%). Repeat attendance at Coping with Pain was associated with reduced characteristic pain intensity and depression, while repeat attendance at Relaxation Training was associated with decreased anxiety. Conclusions Coping with Pain, Relaxation Training, and Group Singing are transportable, affordable, adaptable, and tolerated well by patients with pain and show promise as components of a multimodal pain management approach in methadone maintenance treatment.