Comer S D, Collins E D, Fischman M W
New York State Psychiatric Institute and Department of Psychiatry, College of Physicians and Surgeons of Columbia University, NY 10032, USA.
Psychopharmacology (Berl). 2001 Feb;154(1):28-37. doi: 10.1007/s002130000623.
Studies have shown that buprenorphine, a partial mu opioid agonist, effectively reduces heroin taking. While previous research with buprenorphine utilized a liquid formulation, a tablet formulation is proposed for clinical use. However, because recent research suggests that the liquid and tablet differ in bio-availability, it is unclear what dose of the buprenorphine tablet effectively antagonizes the reinforcing effects of heroin.
The present study was designed to compare the effects of two sublingual doses of buprenorphine maintenance on heroin self-administration.
Eight heroin-dependent men participated in a 6-week, double-blind, placebo-controlled inpatient study to evaluate the reinforcing effects of intravenous heroin (0, 6.25, 12.5, 25 mg) during maintenance on 8 or 16 mg sublingual buprenorphine. Participants first sampled the available dose of heroin, and then were allowed to respond under a progressive ratio schedule for either heroin or $20. For each heroin dose, one sample session and three choice sessions occurred. Two sessions per day were conducted. A sample session was followed by the first choice session on one day, and the second and third choice sessions occurred on the following day. These sessions were conducted while participants were maintained on daily doses of 8 or 16 mg buprenorphine (3 weeks each).
Relative to placebo, 12.5 and 25 mg heroin produced significant increases in break point values under both maintenance dose conditions. The mean break point value for 12.5 mg heroin was significantly lower under 16 mg buprenorphine, compared to 8 mg.
These results demonstrate that the reinforcing effects of heroin were not fully antagonized by these doses of the tablet formulation of buprenorphine, and that 16 mg buprenorphine reduced heroin self-administration relative to 8 mg.
研究表明，丁丙诺啡作为一种μ阿片受体部分激动剂，能有效减少海洛因使用。此前关于丁丙诺啡的研究使用的是液体制剂，现有一种片剂制剂被提议用于临床。然而，由于近期研究表明液体制剂和片剂在生物利用度上存在差异，目前尚不清楚丁丙诺啡片剂的何种剂量能有效拮抗海洛因的强化作用。
本研究旨在比较两种舌下含服剂量的丁丙诺啡维持治疗对海洛因自我给药的影响。
八名海洛因依赖男性参与了一项为期6周的双盲、安慰剂对照住院研究，以评估在舌下含服8毫克或16毫克丁丙诺啡维持治疗期间，静脉注射海洛因（0、6.25、12.5、25毫克）的强化作用。参与者首先对可用剂量的海洛因进行采样，然后在累进比率程序下对海洛因或20美元进行反应。对于每个海洛因剂量，进行一次采样 session 和三次选择 session。每天进行两次 session。一次采样 session 之后，在一天内进行第一次选择 session，第二天进行第二次和第三次选择 session。这些 session 在参与者每日服用8毫克或16毫克丁丙诺啡（各3周）维持治疗期间进行。
相对于安慰剂，在两种维持剂量条件下，12.5毫克和25毫克海洛因均使断点值显著增加。与8毫克丁丙诺啡相比，在16毫克丁丙诺啡维持治疗下，12.5毫克海洛因的平均断点值显著更低。
这些结果表明，这些剂量的丁丙诺啡片剂制剂并未完全拮抗海洛因的强化作用，且与8毫克相比，16毫克丁丙诺啡减少了海洛因的自我给药。
