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Michael Davis - One of the best experts on this subject based on the ideXlab platform.
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Anxiolytic-like effects of morphine and Buprenorphine in the rat model of fear-potentiated startle: tolerance, cross-tolerance, and blockade by naloxone
Psychopharmacology, 2008Co-Authors: Ebony M. Glover, Michael DavisAbstract:Rationale Morphine and Buprenorphine have analgesic and anxiolytic-like properties. While their analgesic effects have been well characterized, their anxiolytic-like properties have not. Objectives Effects of acute morphine and Buprenorphine on the expression of acoustic fear-potentiated startle (FPS) and naloxone pretreatment were assessed. Effects of chronic morphine and Buprenorphine on tolerance, cross-tolerance, and withdrawal were also examined. Materials and methods Fear-conditioned rats were given subcutaneous drug treatment immediately before testing for FPS. Experiment 1, rats were administered morphine (0.03, 0.25, 0.63, 2.5, or 10 mg/kg) or Buprenorphine (0.004, 0.0075, 0.015, 0.03, or 0.25 mg/kg). Experiment 2, rats were given saline or naloxone (0.5 mg/kg) and 5min later given saline, morphine (2.5 mg/kg), or Buprenorphine (0.03 mg/kg). Experiment 3, rats received once-daily injections of saline, morphine (10 mg/kg), or Buprenorphine (0.25 mg/kg) for 7 days. Immediately before testing, saline-treated rats were given saline, morphine (2.5 mg/kg), or Buprenorphine (0.03 mg/kg), morphine-treated rats were given morphine (2.5 mg/kg) or Buprenorphine (0.03 mg/kg), and Buprenorphine-treated rats were given Buprenorphine (0.03 mg/kg) or morphine (2.5 mg/kg). Tolerance and cross-tolerance in analgesia were assessed via the tail-flick test, as were naloxone-precipitated withdrawal. Results Morphine and Buprenorphine had parallel dose–response curves in blocking FPS, with Buprenorphine 40 times more potent than morphine. Naloxone reversed these effects. Morphine and Buprenorphine showed tolerance and cross-tolerance in their anxiolytic-like and analgesic effects. Chronic Buprenorphine produced less withdrawal than chronic morphine. Conclusions Cross-tolerance between morphine and Buprenorphine suggests a common receptor mediating their anxiolytic-like and analgesic effects.
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Anxiolytic-like effects of morphine and Buprenorphine in the rat model of fear-potentiated startle: tolerance, cross-tolerance, and blockade by naloxone
Psychopharmacology, 2008Co-Authors: Ebony M. Glover, Michael DavisAbstract:Rationale Morphine and Buprenorphine have analgesic and anxiolytic-like properties. While their analgesic effects have been well characterized, their anxiolytic-like properties have not. Objectives Effects of acute morphine and Buprenorphine on the expression of acoustic fear-potentiated startle (FPS) and naloxone pretreatment were assessed. Effects of chronic morphine and Buprenorphine on tolerance, cross-tolerance, and withdrawal were also examined. Materials and methods Fear-conditioned rats were given subcutaneous drug treatment immediately before testing for FPS. Experiment 1, rats were administered morphine (0.03, 0.25, 0.63, 2.5, or 10 mg/kg) or Buprenorphine (0.004, 0.0075, 0.015, 0.03, or 0.25 mg/kg). Experiment 2, rats were given saline or naloxone (0.5 mg/kg) and 5min later given saline, morphine (2.5 mg/kg), or Buprenorphine (0.03 mg/kg). Experiment 3, rats received once-daily injections of saline, morphine (10 mg/kg), or Buprenorphine (0.25 mg/kg) for 7 days. Immediately before testing, saline-treated rats were given saline, morphine (2.5 mg/kg), or Buprenorphine (0.03 mg/kg), morphine-treated rats were given morphine (2.5 mg/kg) or Buprenorphine (0.03 mg/kg), and Buprenorphine-treated rats were given Buprenorphine (0.03 mg/kg) or morphine (2.5 mg/kg). Tolerance and cross-tolerance in analgesia were assessed via the tail-flick test, as were naloxone-precipitated withdrawal. Results Morphine and Buprenorphine had parallel dose–response curves in blocking FPS, with Buprenorphine 40 times more potent than morphine. Naloxone reversed these effects. Morphine and Buprenorphine showed tolerance and cross-tolerance in their anxiolytic-like and analgesic effects. Chronic Buprenorphine produced less withdrawal than chronic morphine. Conclusions Cross-tolerance between morphine and Buprenorphine suggests a common receptor mediating their anxiolytic-like and analgesic effects.
George E. Bigelow - One of the best experts on this subject based on the ideXlab platform.
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Acute effects of intramuscular and sublingual Buprenorphine and Buprenorphine/naloxone in non-dependent opioid abusers
Psychopharmacology, 2010Co-Authors: Angela N. Duke, George E. Bigelow, Sharon L. Walsh, Christopher J. Correia, Eric C. StrainAbstract:Rationale Buprenorphine is a partial mu opioid receptor agonist with clinical efficacy as a pharmacotherapy for opioid dependence. A sublingual combination formulation was developed containing Buprenorphine and naloxone with the intent of decreasing abuse liability in opioid-dependent individuals. However, the addition of naloxone may not limit abuse potential of this medication when taken by individuals without opioid physical dependence. Objectives The present study investigated the effects of Buprenorphine alone and in combination with naloxone administered intramuscularly and sublingually to non-dependent opioid abusers. Methods In a within-subject crossover design, non-dependent opioid-experienced volunteers ( N = 8) were administered acute doses of Buprenorphine (4, 8, and 16 mg) and Buprenorphine/naloxone (4/1, 8/2, and 16/4 mg) via both intramuscular and sublingual routes, intramuscular hydromorphone (2 and 4 mg as an opioid agonist control), and placebo, for a total of 15 drug conditions. Laboratory sessions were conducted twice per week using a double-blind, double-dummy design. Results Buprenorphine and Buprenorphine/naloxone engendered effects similar to hydromorphone. Intramuscular administration produced a greater magnitude of effects compared to the sublingual route at the intermediate dose of Buprenorphine and at both the low and high doses of the Buprenorphine/naloxone combination. The addition of naloxone did not significantly alter the effects of Buprenorphine. Conclusions These results suggest that Buprenorphine and Buprenorphine/naloxone have similar abuse potential in non-dependent opioid abusers, and that the addition of naloxone at these doses and in this dose ratio confers no evident advantage for decreasing the abuse potential of intramuscular or sublingual Buprenorphine in this population.
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Blockade of hydromorphone effects by Buprenorphine/naloxone and Buprenorphine
Psychopharmacology, 2001Co-Authors: Eric C. Strain, Sharon L. Walsh, George E. BigelowAbstract:Rationale: Buprenorphine is an opioid agonist–antagonist used in the treatment of opioid dependence. Naloxone has been combined with Buprenorphine to decrease the parenteral abuse potential of Buprenorphine. This addition of naloxone may also confer further opioid blockade efficacy. Objectives: To test the opioid blockade efficacy of sublingual Buprenorphine/naloxone versus Buprenorphine alone and determine whether: (1) the blockade efficacy of Buprenorphine/naloxone varies between the time of expected maximal and minimal effects of naloxone, (2) the blockade efficacy of Buprenorphine/naloxone and Buprenorphine varies as a function of maintenance dose level, and (3) there are adaptive changes over time associated with repeated daily dosing of Buprenorphine/naloxone and Buprenorphine. Methods: Residential subjects (n=6) were maintained on different double-blind dose levels of Buprenorphine/naloxone (4/1, 8/2, 16/4, 32/8 mg) and Buprenorphine (32 mg) for 6-day periods and challenged with parenteral doses of hydromorphone (12 mg) in laboratory sessions. Results: There was no evidence of additional opioid blockade efficacy conferred by combining naloxone with Buprenorphine. Higher doses of Buprenorphine/naloxone provided greater blockade of hydromorphone effects. Changes over time associated with repeated daily dosing of Buprenorphine/naloxone and Buprenorphine were minimal. Conclusions: The addition of naloxone to Buprenorphine may deter the parenteral abuse of Buprenorphine/naloxone, but it does not enhance the therapeutic efficacy of Buprenorphine. The blockade efficacy of Buprenorphine/naloxone is dose related; however, doses up to 32/8 mg Buprenorphine/naloxone provide only partial blockade when subjects receive a high dose of an opioid agonist.
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Effects of Buprenorphine versus Buprenorphine/naloxone tablets in non- dependent opioid abusers
Psychopharmacology, 2000Co-Authors: Eric C. Strain, Kenneth B. Stoller, Sharon L. Walsh, George E. BigelowAbstract:Rationale: Buprenorphine is an opioid agonist-antagonist under development in the United States as a sublingual medication for treatment of opioid dependence. Buprenorphine may be abused; therefore, tablets combining Buprenorphine with naloxone have been developed with the intent of reducing the abuse risk in people physically dependent upon opioids. The characteristics and abuse potential of Buprenorphine and Buprenorphine/naloxone tablets in non-dependent opioid abusers have not been determined. Non-parenteral abuse of opioids such as Buprenorphine may be more likely in people who have less severe substance abuse disorders (e.g., are not physically dependent upon opioids). Objectives: To assess the abuse potential of sublingual Buprenorphine and Buprenorphine/naloxone tablets in non-dependent opioid abusers. Methods: Subjects (n=7) were tested with sublingual Buprenorphine (4, 8, 16 mg), sublingual Buprenorphine/naloxone (1/0.25, 2/0.5, 4/1, 8/2, 16/4 mg), as well as intramuscular hydromorphone as an opioid agonist control (2, 4 mg) and placebo in laboratory sessions conducted twice per week. Dosing was double-blind and double-dummy. Results: The higher doses of both Buprenorphine and Buprenorphine/naloxone produced similar opioid agonist-like effects. The onset of these effects was slowed, consistent with the sublingual route of administration, and the magnitude of effects was moderate. There was no evidence to suggest the addition of naloxone attenuated Buprenorphine’s opioid agonist effects in this population when Buprenorphine was delivered by the sublingual route. Conclusions: These results suggest that sublingual Buprenorphine and Buprenorphine/naloxone may both be abused by opioid users who are not physically dependent upon opioids.
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The effects of Buprenorphine in Buprenorphine-maintained volunteers
Psychopharmacology, 1997Co-Authors: Eric C. Strain, Sharon L. Walsh, Kenzie L. Preston, Ira A. Liebson, George E. BigelowAbstract:Buprenorphine is a mu opioid partial agonist currently used as an analgesic, and being developed for the treatment of opioid dependence. The purpose of this study was to determine the abuse liability of parenteral Buprenorphine in volunteers maintained on daily sublingual (SL) Buprenorphine (8 mg). In a residential laboratory, eight volunteers underwent pharmacologic challenges two times per week. Medication challenges were 16 h after the daily dose of Buprenorphine, and consisted of double-blind IM injections of Buprenorphine (4, 8, 16 mg), the prototypic mu opioid agonist hydromorphone (9 and 18 mg), or saline. Assessments consisted of physiologic monitoring, subjects' self-reports, and a trained observer's ratings of drug effects, and were collected for 0.5 h before and 2.0 h following injection. Supplemental doses of IM Buprenorphine produced opioid agonist-like effects, indicating some abuse potential of parenteral Buprenorphine in Buprenorphine-maintained patients. There was incomplete cross-tolerance to the effects of hydromorphone, suggesting that higher maintenance doses of Buprenorphine may be needed to maximize clinical efficacy. However, there was a lack of graded dose-effects for hydromorphone, suggesting that Buprenorphine's combination of partial agonist effects and high affinity for opioid receptors may limit the magnitude of effects of supplemental full agonists. Finally, participants tolerated cumulative doses of maintenance Buprenorphine plus challenge Buprenorphine without adverse effects, suggesting higher doses of Buprenorphine can be safely administered to opioid dependent patients.
Eric C. Strain - One of the best experts on this subject based on the ideXlab platform.
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Acute effects of intramuscular and sublingual Buprenorphine and Buprenorphine/naloxone in non-dependent opioid abusers
Psychopharmacology, 2010Co-Authors: Angela N. Duke, George E. Bigelow, Sharon L. Walsh, Christopher J. Correia, Eric C. StrainAbstract:Rationale Buprenorphine is a partial mu opioid receptor agonist with clinical efficacy as a pharmacotherapy for opioid dependence. A sublingual combination formulation was developed containing Buprenorphine and naloxone with the intent of decreasing abuse liability in opioid-dependent individuals. However, the addition of naloxone may not limit abuse potential of this medication when taken by individuals without opioid physical dependence. Objectives The present study investigated the effects of Buprenorphine alone and in combination with naloxone administered intramuscularly and sublingually to non-dependent opioid abusers. Methods In a within-subject crossover design, non-dependent opioid-experienced volunteers ( N = 8) were administered acute doses of Buprenorphine (4, 8, and 16 mg) and Buprenorphine/naloxone (4/1, 8/2, and 16/4 mg) via both intramuscular and sublingual routes, intramuscular hydromorphone (2 and 4 mg as an opioid agonist control), and placebo, for a total of 15 drug conditions. Laboratory sessions were conducted twice per week using a double-blind, double-dummy design. Results Buprenorphine and Buprenorphine/naloxone engendered effects similar to hydromorphone. Intramuscular administration produced a greater magnitude of effects compared to the sublingual route at the intermediate dose of Buprenorphine and at both the low and high doses of the Buprenorphine/naloxone combination. The addition of naloxone did not significantly alter the effects of Buprenorphine. Conclusions These results suggest that Buprenorphine and Buprenorphine/naloxone have similar abuse potential in non-dependent opioid abusers, and that the addition of naloxone at these doses and in this dose ratio confers no evident advantage for decreasing the abuse potential of intramuscular or sublingual Buprenorphine in this population.
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Buprenorphine: how to use it right.
Drug and alcohol dependence, 2003Co-Authors: Rolley E Johnson, Eric C. Strain, Leslie AmassAbstract:The unique pharmacology of Buprenorphine at the mu-opioid receptor (i.e. high affinity, low intrinsic activity and slow dissociation) results in Buprenorphine having: (1) a good safety profile, (2) low physical dependence, and (3) flexibility in dose scheduling. Early studies assessed the effectiveness of Buprenorphine for the treatment of opioid dependence using a sublingual solution formulation. More recently, a combination tablet (Buprenorphine/naloxone in a 4:1 ratio) has been assessed with the goal of decreasing diversion and abuse. Controlled studies with Buprenorphine solution, Buprenorphine mono-tablet, and Buprenorphine/naloxone combination tablet have uniformly demonstrated the effectiveness of Buprenorphine for opioid dependence treatment and the combination tablet appears to decrease (but not eliminate) abuse potential. There is general agreement across studies regarding Buprenorphine induction and maintenance dose schedules. The clinical effects of Buprenorphine and Buprenorphine/naloxone are similar and most patients can be treated initially with and maintained on a daily Buprenorphine/naloxone dose of 4:1-24:6 mg. Dosing is possible on a less-than-daily schedule; however, multiples of the daily-dose should be administered to cover the increased interval between doses. If Buprenorphine withdrawal is indicated, gradual dose reduction is recommended over a rapid dose reduction or abrupt cessation. Both tablet formulations are approved by the US FDA for opioid dependence treatment as Schedule III narcotics and are, therefore, available for use in office-based practice. The Buprenorphine plus naloxone combination product should provide additional safeguards for use in office-based practice by decreasing risk of diversion, and office-based treatment should expand the availability of services to opioid dependent patients.
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Blockade of hydromorphone effects by Buprenorphine/naloxone and Buprenorphine
Psychopharmacology, 2001Co-Authors: Eric C. Strain, Sharon L. Walsh, George E. BigelowAbstract:Rationale: Buprenorphine is an opioid agonist–antagonist used in the treatment of opioid dependence. Naloxone has been combined with Buprenorphine to decrease the parenteral abuse potential of Buprenorphine. This addition of naloxone may also confer further opioid blockade efficacy. Objectives: To test the opioid blockade efficacy of sublingual Buprenorphine/naloxone versus Buprenorphine alone and determine whether: (1) the blockade efficacy of Buprenorphine/naloxone varies between the time of expected maximal and minimal effects of naloxone, (2) the blockade efficacy of Buprenorphine/naloxone and Buprenorphine varies as a function of maintenance dose level, and (3) there are adaptive changes over time associated with repeated daily dosing of Buprenorphine/naloxone and Buprenorphine. Methods: Residential subjects (n=6) were maintained on different double-blind dose levels of Buprenorphine/naloxone (4/1, 8/2, 16/4, 32/8 mg) and Buprenorphine (32 mg) for 6-day periods and challenged with parenteral doses of hydromorphone (12 mg) in laboratory sessions. Results: There was no evidence of additional opioid blockade efficacy conferred by combining naloxone with Buprenorphine. Higher doses of Buprenorphine/naloxone provided greater blockade of hydromorphone effects. Changes over time associated with repeated daily dosing of Buprenorphine/naloxone and Buprenorphine were minimal. Conclusions: The addition of naloxone to Buprenorphine may deter the parenteral abuse of Buprenorphine/naloxone, but it does not enhance the therapeutic efficacy of Buprenorphine. The blockade efficacy of Buprenorphine/naloxone is dose related; however, doses up to 32/8 mg Buprenorphine/naloxone provide only partial blockade when subjects receive a high dose of an opioid agonist.
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Effects of Buprenorphine versus Buprenorphine/naloxone tablets in non- dependent opioid abusers
Psychopharmacology, 2000Co-Authors: Eric C. Strain, Kenneth B. Stoller, Sharon L. Walsh, George E. BigelowAbstract:Rationale: Buprenorphine is an opioid agonist-antagonist under development in the United States as a sublingual medication for treatment of opioid dependence. Buprenorphine may be abused; therefore, tablets combining Buprenorphine with naloxone have been developed with the intent of reducing the abuse risk in people physically dependent upon opioids. The characteristics and abuse potential of Buprenorphine and Buprenorphine/naloxone tablets in non-dependent opioid abusers have not been determined. Non-parenteral abuse of opioids such as Buprenorphine may be more likely in people who have less severe substance abuse disorders (e.g., are not physically dependent upon opioids). Objectives: To assess the abuse potential of sublingual Buprenorphine and Buprenorphine/naloxone tablets in non-dependent opioid abusers. Methods: Subjects (n=7) were tested with sublingual Buprenorphine (4, 8, 16 mg), sublingual Buprenorphine/naloxone (1/0.25, 2/0.5, 4/1, 8/2, 16/4 mg), as well as intramuscular hydromorphone as an opioid agonist control (2, 4 mg) and placebo in laboratory sessions conducted twice per week. Dosing was double-blind and double-dummy. Results: The higher doses of both Buprenorphine and Buprenorphine/naloxone produced similar opioid agonist-like effects. The onset of these effects was slowed, consistent with the sublingual route of administration, and the magnitude of effects was moderate. There was no evidence to suggest the addition of naloxone attenuated Buprenorphine’s opioid agonist effects in this population when Buprenorphine was delivered by the sublingual route. Conclusions: These results suggest that sublingual Buprenorphine and Buprenorphine/naloxone may both be abused by opioid users who are not physically dependent upon opioids.
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The effects of Buprenorphine in Buprenorphine-maintained volunteers
Psychopharmacology, 1997Co-Authors: Eric C. Strain, Sharon L. Walsh, Kenzie L. Preston, Ira A. Liebson, George E. BigelowAbstract:Buprenorphine is a mu opioid partial agonist currently used as an analgesic, and being developed for the treatment of opioid dependence. The purpose of this study was to determine the abuse liability of parenteral Buprenorphine in volunteers maintained on daily sublingual (SL) Buprenorphine (8 mg). In a residential laboratory, eight volunteers underwent pharmacologic challenges two times per week. Medication challenges were 16 h after the daily dose of Buprenorphine, and consisted of double-blind IM injections of Buprenorphine (4, 8, 16 mg), the prototypic mu opioid agonist hydromorphone (9 and 18 mg), or saline. Assessments consisted of physiologic monitoring, subjects' self-reports, and a trained observer's ratings of drug effects, and were collected for 0.5 h before and 2.0 h following injection. Supplemental doses of IM Buprenorphine produced opioid agonist-like effects, indicating some abuse potential of parenteral Buprenorphine in Buprenorphine-maintained patients. There was incomplete cross-tolerance to the effects of hydromorphone, suggesting that higher maintenance doses of Buprenorphine may be needed to maximize clinical efficacy. However, there was a lack of graded dose-effects for hydromorphone, suggesting that Buprenorphine's combination of partial agonist effects and high affinity for opioid receptors may limit the magnitude of effects of supplemental full agonists. Finally, participants tolerated cumulative doses of maintenance Buprenorphine plus challenge Buprenorphine without adverse effects, suggesting higher doses of Buprenorphine can be safely administered to opioid dependent patients.
Ebony M. Glover - One of the best experts on this subject based on the ideXlab platform.
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Anxiolytic-like effects of morphine and Buprenorphine in the rat model of fear-potentiated startle: tolerance, cross-tolerance, and blockade by naloxone
Psychopharmacology, 2008Co-Authors: Ebony M. Glover, Michael DavisAbstract:Rationale Morphine and Buprenorphine have analgesic and anxiolytic-like properties. While their analgesic effects have been well characterized, their anxiolytic-like properties have not. Objectives Effects of acute morphine and Buprenorphine on the expression of acoustic fear-potentiated startle (FPS) and naloxone pretreatment were assessed. Effects of chronic morphine and Buprenorphine on tolerance, cross-tolerance, and withdrawal were also examined. Materials and methods Fear-conditioned rats were given subcutaneous drug treatment immediately before testing for FPS. Experiment 1, rats were administered morphine (0.03, 0.25, 0.63, 2.5, or 10 mg/kg) or Buprenorphine (0.004, 0.0075, 0.015, 0.03, or 0.25 mg/kg). Experiment 2, rats were given saline or naloxone (0.5 mg/kg) and 5min later given saline, morphine (2.5 mg/kg), or Buprenorphine (0.03 mg/kg). Experiment 3, rats received once-daily injections of saline, morphine (10 mg/kg), or Buprenorphine (0.25 mg/kg) for 7 days. Immediately before testing, saline-treated rats were given saline, morphine (2.5 mg/kg), or Buprenorphine (0.03 mg/kg), morphine-treated rats were given morphine (2.5 mg/kg) or Buprenorphine (0.03 mg/kg), and Buprenorphine-treated rats were given Buprenorphine (0.03 mg/kg) or morphine (2.5 mg/kg). Tolerance and cross-tolerance in analgesia were assessed via the tail-flick test, as were naloxone-precipitated withdrawal. Results Morphine and Buprenorphine had parallel dose–response curves in blocking FPS, with Buprenorphine 40 times more potent than morphine. Naloxone reversed these effects. Morphine and Buprenorphine showed tolerance and cross-tolerance in their anxiolytic-like and analgesic effects. Chronic Buprenorphine produced less withdrawal than chronic morphine. Conclusions Cross-tolerance between morphine and Buprenorphine suggests a common receptor mediating their anxiolytic-like and analgesic effects.
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Anxiolytic-like effects of morphine and Buprenorphine in the rat model of fear-potentiated startle: tolerance, cross-tolerance, and blockade by naloxone
Psychopharmacology, 2008Co-Authors: Ebony M. Glover, Michael DavisAbstract:Rationale Morphine and Buprenorphine have analgesic and anxiolytic-like properties. While their analgesic effects have been well characterized, their anxiolytic-like properties have not. Objectives Effects of acute morphine and Buprenorphine on the expression of acoustic fear-potentiated startle (FPS) and naloxone pretreatment were assessed. Effects of chronic morphine and Buprenorphine on tolerance, cross-tolerance, and withdrawal were also examined. Materials and methods Fear-conditioned rats were given subcutaneous drug treatment immediately before testing for FPS. Experiment 1, rats were administered morphine (0.03, 0.25, 0.63, 2.5, or 10 mg/kg) or Buprenorphine (0.004, 0.0075, 0.015, 0.03, or 0.25 mg/kg). Experiment 2, rats were given saline or naloxone (0.5 mg/kg) and 5min later given saline, morphine (2.5 mg/kg), or Buprenorphine (0.03 mg/kg). Experiment 3, rats received once-daily injections of saline, morphine (10 mg/kg), or Buprenorphine (0.25 mg/kg) for 7 days. Immediately before testing, saline-treated rats were given saline, morphine (2.5 mg/kg), or Buprenorphine (0.03 mg/kg), morphine-treated rats were given morphine (2.5 mg/kg) or Buprenorphine (0.03 mg/kg), and Buprenorphine-treated rats were given Buprenorphine (0.03 mg/kg) or morphine (2.5 mg/kg). Tolerance and cross-tolerance in analgesia were assessed via the tail-flick test, as were naloxone-precipitated withdrawal. Results Morphine and Buprenorphine had parallel dose–response curves in blocking FPS, with Buprenorphine 40 times more potent than morphine. Naloxone reversed these effects. Morphine and Buprenorphine showed tolerance and cross-tolerance in their anxiolytic-like and analgesic effects. Chronic Buprenorphine produced less withdrawal than chronic morphine. Conclusions Cross-tolerance between morphine and Buprenorphine suggests a common receptor mediating their anxiolytic-like and analgesic effects.
Sharon L. Walsh - One of the best experts on this subject based on the ideXlab platform.
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Acute effects of intramuscular and sublingual Buprenorphine and Buprenorphine/naloxone in non-dependent opioid abusers
Psychopharmacology, 2010Co-Authors: Angela N. Duke, George E. Bigelow, Sharon L. Walsh, Christopher J. Correia, Eric C. StrainAbstract:Rationale Buprenorphine is a partial mu opioid receptor agonist with clinical efficacy as a pharmacotherapy for opioid dependence. A sublingual combination formulation was developed containing Buprenorphine and naloxone with the intent of decreasing abuse liability in opioid-dependent individuals. However, the addition of naloxone may not limit abuse potential of this medication when taken by individuals without opioid physical dependence. Objectives The present study investigated the effects of Buprenorphine alone and in combination with naloxone administered intramuscularly and sublingually to non-dependent opioid abusers. Methods In a within-subject crossover design, non-dependent opioid-experienced volunteers ( N = 8) were administered acute doses of Buprenorphine (4, 8, and 16 mg) and Buprenorphine/naloxone (4/1, 8/2, and 16/4 mg) via both intramuscular and sublingual routes, intramuscular hydromorphone (2 and 4 mg as an opioid agonist control), and placebo, for a total of 15 drug conditions. Laboratory sessions were conducted twice per week using a double-blind, double-dummy design. Results Buprenorphine and Buprenorphine/naloxone engendered effects similar to hydromorphone. Intramuscular administration produced a greater magnitude of effects compared to the sublingual route at the intermediate dose of Buprenorphine and at both the low and high doses of the Buprenorphine/naloxone combination. The addition of naloxone did not significantly alter the effects of Buprenorphine. Conclusions These results suggest that Buprenorphine and Buprenorphine/naloxone have similar abuse potential in non-dependent opioid abusers, and that the addition of naloxone at these doses and in this dose ratio confers no evident advantage for decreasing the abuse potential of intramuscular or sublingual Buprenorphine in this population.
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Blockade of hydromorphone effects by Buprenorphine/naloxone and Buprenorphine
Psychopharmacology, 2001Co-Authors: Eric C. Strain, Sharon L. Walsh, George E. BigelowAbstract:Rationale: Buprenorphine is an opioid agonist–antagonist used in the treatment of opioid dependence. Naloxone has been combined with Buprenorphine to decrease the parenteral abuse potential of Buprenorphine. This addition of naloxone may also confer further opioid blockade efficacy. Objectives: To test the opioid blockade efficacy of sublingual Buprenorphine/naloxone versus Buprenorphine alone and determine whether: (1) the blockade efficacy of Buprenorphine/naloxone varies between the time of expected maximal and minimal effects of naloxone, (2) the blockade efficacy of Buprenorphine/naloxone and Buprenorphine varies as a function of maintenance dose level, and (3) there are adaptive changes over time associated with repeated daily dosing of Buprenorphine/naloxone and Buprenorphine. Methods: Residential subjects (n=6) were maintained on different double-blind dose levels of Buprenorphine/naloxone (4/1, 8/2, 16/4, 32/8 mg) and Buprenorphine (32 mg) for 6-day periods and challenged with parenteral doses of hydromorphone (12 mg) in laboratory sessions. Results: There was no evidence of additional opioid blockade efficacy conferred by combining naloxone with Buprenorphine. Higher doses of Buprenorphine/naloxone provided greater blockade of hydromorphone effects. Changes over time associated with repeated daily dosing of Buprenorphine/naloxone and Buprenorphine were minimal. Conclusions: The addition of naloxone to Buprenorphine may deter the parenteral abuse of Buprenorphine/naloxone, but it does not enhance the therapeutic efficacy of Buprenorphine. The blockade efficacy of Buprenorphine/naloxone is dose related; however, doses up to 32/8 mg Buprenorphine/naloxone provide only partial blockade when subjects receive a high dose of an opioid agonist.
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Effects of Buprenorphine versus Buprenorphine/naloxone tablets in non- dependent opioid abusers
Psychopharmacology, 2000Co-Authors: Eric C. Strain, Kenneth B. Stoller, Sharon L. Walsh, George E. BigelowAbstract:Rationale: Buprenorphine is an opioid agonist-antagonist under development in the United States as a sublingual medication for treatment of opioid dependence. Buprenorphine may be abused; therefore, tablets combining Buprenorphine with naloxone have been developed with the intent of reducing the abuse risk in people physically dependent upon opioids. The characteristics and abuse potential of Buprenorphine and Buprenorphine/naloxone tablets in non-dependent opioid abusers have not been determined. Non-parenteral abuse of opioids such as Buprenorphine may be more likely in people who have less severe substance abuse disorders (e.g., are not physically dependent upon opioids). Objectives: To assess the abuse potential of sublingual Buprenorphine and Buprenorphine/naloxone tablets in non-dependent opioid abusers. Methods: Subjects (n=7) were tested with sublingual Buprenorphine (4, 8, 16 mg), sublingual Buprenorphine/naloxone (1/0.25, 2/0.5, 4/1, 8/2, 16/4 mg), as well as intramuscular hydromorphone as an opioid agonist control (2, 4 mg) and placebo in laboratory sessions conducted twice per week. Dosing was double-blind and double-dummy. Results: The higher doses of both Buprenorphine and Buprenorphine/naloxone produced similar opioid agonist-like effects. The onset of these effects was slowed, consistent with the sublingual route of administration, and the magnitude of effects was moderate. There was no evidence to suggest the addition of naloxone attenuated Buprenorphine’s opioid agonist effects in this population when Buprenorphine was delivered by the sublingual route. Conclusions: These results suggest that sublingual Buprenorphine and Buprenorphine/naloxone may both be abused by opioid users who are not physically dependent upon opioids.
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The effects of Buprenorphine in Buprenorphine-maintained volunteers
Psychopharmacology, 1997Co-Authors: Eric C. Strain, Sharon L. Walsh, Kenzie L. Preston, Ira A. Liebson, George E. BigelowAbstract:Buprenorphine is a mu opioid partial agonist currently used as an analgesic, and being developed for the treatment of opioid dependence. The purpose of this study was to determine the abuse liability of parenteral Buprenorphine in volunteers maintained on daily sublingual (SL) Buprenorphine (8 mg). In a residential laboratory, eight volunteers underwent pharmacologic challenges two times per week. Medication challenges were 16 h after the daily dose of Buprenorphine, and consisted of double-blind IM injections of Buprenorphine (4, 8, 16 mg), the prototypic mu opioid agonist hydromorphone (9 and 18 mg), or saline. Assessments consisted of physiologic monitoring, subjects' self-reports, and a trained observer's ratings of drug effects, and were collected for 0.5 h before and 2.0 h following injection. Supplemental doses of IM Buprenorphine produced opioid agonist-like effects, indicating some abuse potential of parenteral Buprenorphine in Buprenorphine-maintained patients. There was incomplete cross-tolerance to the effects of hydromorphone, suggesting that higher maintenance doses of Buprenorphine may be needed to maximize clinical efficacy. However, there was a lack of graded dose-effects for hydromorphone, suggesting that Buprenorphine's combination of partial agonist effects and high affinity for opioid receptors may limit the magnitude of effects of supplemental full agonists. Finally, participants tolerated cumulative doses of maintenance Buprenorphine plus challenge Buprenorphine without adverse effects, suggesting higher doses of Buprenorphine can be safely administered to opioid dependent patients.
