Aceto and Bowman (1993) | Buspirone (0.2, 0.4, and 0.8 mg/kg) | Rhesus Monkey | ≥3 | Precipitated, naloxone (0.05 mg/kg, s.c.) 2 to 3 hours after last morphine administration | Morphine (3 mg/kg, s.c.) at minimum for ≥3 months | Ataxia, body sag, fighting, jaw sag, lying down, ptosis, retching, restlessness, rigid abdominal muscles, slowing, vocalization, and wet dog shakes | Buspirone dose dependently reduced rigid abdominal muscles, fighting, lying down, retching, restlessness, and vocalization and increased wet dog shakes. |
Berthold et al. (1989) | Clonidine (0.01, 0.03, 0.1, and 0.3 mg/kg), prazosin (0.1, 1, and 4 mg/kg), spiroperidol (0.05 and 0.5 mg/kg), 8-OH-DPAT (0.5, 1, 2, 4, 8 mg/kg); RU 24969 fumerate (0.125, 0.25, 0.5., 1, 2, and 4 mg/kg); Idazoxan; (−)-pindolol (1, 2, and 4 mglkg); (+)-SDZ 21-009 (1 mg/kg); (−)-SDZ 21-009 (1 mg/kg); buspironc (1, 2, 5, and 10 mg/kg); ipsapirone (1, 3, and 10 mg/kg); yohimbine (0.5 and 2 mg/kg); flesinoxan (0.5, 1, and 3 mg/kg); Rauwolscine (0.5 and 2 mg/kg), WY 26392 (0.5, 2 mg/kg), haloperidol (0.1, 0.5, and 1.0 mg/kg); pCPA (150 mg/kg). Administered subcutaneously. | Mouse | 10 | Precipitated, naloxone (1 mg/kg, i.p.) on day 5 | Morphine (75 mg) subcutaneous implant for 5 days | Jumping | 8-OH-DPAT (1 mg/kg), RU 24969 (0.25–4 mg/kg), buspirone (2 mg/kg) (5-HT1 agonists), ipsapirone (10 mg/kg), and flesinoxan (all doses) (5-HT1 agonists) decreased jumping. Idazoxan (all doses), prazosin (1 and 4 mg/kg), rauwolscine (2 mg/kg), WY 26392 (all doses), and yohimbine (all doses) (α-adrenoreceptor antagonists) also decreased jumping. Spiroperidol (5-HT1 antagonist) pretreatment had no effect alone but increased jumping from 8-OH-DPAT and buspirone; no effect of spiroperidol pretreatment on RU24969 and idazoxan. Haloperidol pretreatment enhanced 8-OH-DAPAT–related jumping. Pretreatment (−)-pindolol and (−)-SDZ 21-009 (β-adrenoreceptor/5-HT1A and 5-HT1B antagonists) decreased ability of RU 24969 to suppress jumping. (+)-SDZ21-009 did not impact RU 24969. 8-OH-DAPAT unaffected by (−)-pindolol. pCPA, clonidine (α2 agonist), and (−)-pindolol had no effects. |
Cappendijk et al. (1994) | β-Carboline (20 mg/kg), Ibogaine (40 mg/kg). Administered intraperitoneally. | Rat | 10 | Precipitated, naloxone (4 mg/kg, i.p.) on day 3 | Morphine (75 mg) subcutaneous implant for 3 days | Chewing, diarrhea, grooming, jumping, penile licking, ptosis, rearing, rhinorrhea, teeth- chattering, wet dog shakes, vocalization on touch, and total withdrawal score | β-Carboline (20 mg/kg) decreased the total withdrawal score, chewing, diarrhea, grooming penile licking, rearing, and teeth chattering. Ibogaine decreased the total withdrawal score, chewing, diarrhea, penile licking, and teeth chattering. |
Dzoljic et al. (1988) | Ibogaine (4, 8, and 16 μg). Administered intracerebroventricularly. | Rat | 10 | Precipitated, naloxone (5 mg/kg, i.p.) on day 3 | Morphine (85 mg) subcutaneous implant for 3 days | Chewing, diarrhea, digging, ejaculation, grooming, head holding, head shakes, jumping, paw tremor, penile licking, ptosis, rearing, rhinorrhea, salivation, scratching, stretching, teeth chattering, urination, vocalization on touch, wet dog shakes, and writhing | Ibogaine significantly reduced jumping and salivation (8 and 16 μg), chewing, digging, head hiding, penile licking, rearing, teeth chattering, and writhing (all doses), relative to cerebrospinal fluid control condition. |
Francés et al. (1992) | Ibogaine (30 mg/kg). Administered intraperitoneally. | Mouse | 5–32 | Precipitated, naloxone (5 mg/kg, i.p.) on day 1, 2, 3, 4, or 5 (varied based on group) | Escalating morphine doses up to 100 mg/kg, i.p., for up to 5 days (varied based on group) | Body shakes, body weight, dropping, diarrhea, and jumping | Ibogaine (30 mg/kg) increased jumping and did not decrease any withdrawal signs. |
Glick et al. (1992) | Ibogaine (20, 40, and 80 mg/kg). Administered intraperitoneally. | Rat | 7–17 | Precipitated, naltrexone (1 mg/kg, i.p.) on day 6 | Morphine (50 mg) subcutaneous implant for 5 days | Burying, diarrhea, grooming, paw shaking, teeth chattering, and wet dog shakes | Ibogaine decreased diarrhea, teeth chattering, and wet dog shakes (40, 80 mg/kg), and grooming (all doses). |
Hine et al. (1975a) | Cannabidiol (10 mg, kg). Administered intraperitoneally | Rat | 7 | Precipitated, naloxone (4 mg/kg, i.p.) on day 3 | Morphine (75 mg) subcutaneous implant for 3 days | Abnormal posture, chewing, defecation, diarrhea, ear blanching, ptosis, teeth chattering, vocalization, wet dog shakes, and total withdrawal score | Cannabidiol (10 mg/kg) had no effect. |
Hine et al. (1975c) | THC (2 mg/kg), cannabidiol (10 mg/kg), THC (2 mg/kg) + Cannabidiol (10 mg/kg). Administered intraperitoneally. | Rat | 8 to 9 | Precipitated, naloxone (4 mg/kg, i.p.) on day 3 | Morphine (75 mg) subcutaneous implant for 3 days | Abnormal posture, audible grinding, chewing, defecation, escapes, diarrhea, ear blanching, ptosis, teeth chattering, vocalization on touch, wet dog shakes, and writhing | THC (2 mg/kg) decreased total withdrawal scores and defecation, and diarrhea. Cannabidiol alone had no effect. THC (2 mg/kg) + Cannabidiol (10 mg/kg) decreased total withdrawal scores, defecation, ear blanching, escapes, and wet dog shakes. |
Kang et al. (2008) | Mirtazapine (3, 10, and 30 mg/kg). Administered intraperitoneally. | Rat | 40 | Precipitated, naloxone (1 mg/kg, i.p.) on day 10 | Morphine 10 mg, s.c., twice a day for 10 days | Body weight, chewing, digging, escape attendance, grooming, rearing, scratching, teeth chattering, and wet dog shakes | Mirtazapine reduced chewing (10 and 30 mg/kg), and escape attendance, grooming, and teeth chattering (all doses). Mirtazepine (10 and 30 mg/kg) reduced total withdrawal score. |
Koyuncuoğlu et al. (1990) | Ketamine (0.5 and 1 mg/kg, i.v.), dextromethorphan (1 and 2 mg/kg, i.p.). | Rat | 10–16 | Precipitated, naloxone (2 mg/kg, i.p.) on day 3 | Morphine (225 mg) subcutaneous implant + F16 for 3 days | Defecation, diarrhea, flying jumping, ptosis, teeth chattering, wet dog shakes, and writhing | Ketamine (1 mg/kg) decreased defecation, jumping, and teeth chattering, but increased wet dog shakes. Dextromethorphan (1 mg/kg) decreased flying and teeth chattering, and (2 mg/kg) decreased all signs except writhing. |
Leal et al. (2003) | Ibogaine (40 and 80 mg/kg), MK-801 (0.15 and 0.3 mg/kg), ibogaine (40 mg/kg) + MK-801 (0.15 mg/kg). Administered intraperitoneally. | Mouse | 10–13 | Precipitated, naloxone (5 mg/kg, i.p.) on day 4 | Escalating morphine doses up to 225 mg/kg, i.p., by day 3 | Jumping | All doses of ibogaine and MK-801 (NMDA antagonist) decreased jumping. Ibogaine (40 mg/kg) and MK-801 (0.15 mg/kg) coadministration decreased jumping at the level observed for the high dose of each drug independently. |
Lu et al. (2001) | Venlafaxine (10 and 20 mg/kg). Administered intraperitoneally. | Rat | 12 | Precipitated, naloxone (2 mg/kg, i.p.) on day 5 | Escalating morphine doses up to 40 mg/kg, s.c., by day 5 | Body weight, diarrhea, exploring, irritability, jumping, lacrimation, piloerection, ptosis, teeth chattering, wet dog shakes, and writhing | Venlafaxine (10 and 20 mg/kg) decreased diarrhea, exploring, jumping, piloerection, and shakes. Venlafaxine (20 mg/kg per kilogram) also decreased irritability, lacrimation, wet dog shakes, and writhing. |
Mash et al. (2016) | Noribogaine (10, 30, 56, and 100 mg/kg). Intragastric administration | Mouse | 5–11 | Precipitated, naloxone (3 mg/kg, i.p.) on day 4 | Escalating morphine doses up to 75 mg/kg, s.c., for 4 days | Body tremors, diarrhea, jumping, and paw tremors | Noribogaine decreased body tremors (30 and 100 mg/kg), paw tremors (100 mg/kg), and jumping (30, 56, and 100 mg/kg). |
Panchal et al. (2005) | 18-MC (5, 10, and 25 μg/1 μl). Infused into intramedial habenula, locus coeruleus, or interpeduncular nucleus. | Rat | 5–10 | Precipitated, naltrexone (1 mg/kg, i.p.) on day 8 (immediately following intracerebral drug infusion) | Escalating morphine doses up to 80 mg/kg, s.c., 7 days | Burying, diarrhea, grooming, rearing, teeth chattering, and wet dog shakes | Intramedial habenula 18-MC decreased body weight loss (10 μg) and burying (10 μg). Teeth chattering decreased at 5 μg and increased at 10 μg. Intralocus coeruleus 18-MC dose decreased diarrhea (10 μg), burying (all doses), teeth chattering (5 and 20 μg), and wet dog shakes (10 μg). Intrainterpeduncular nucleus 18-MC decreased burying (5 μg) and rearing (10 μg) and increased diarrhea (5 μg) and teeth chattering (20 μg). |
Parker and Siegel (2001) | Ibogaine (40 mg/kg). Administered intraperitoneally. | Rat | 28 total (individual group size NR) | Precipitated, naloxone (1 mg/kg, s.c.) on day 3 | Morphine (20 mg/ml) subcutaneous implant for 2 days | Mouth movements, penile licking, rearing, teeth chattering, and wet dog shakes | Ibogaine (40 mg/kg) decreased mouth movements, penile licking, and teeth chattering. |
Rho and Glick (1998) | 18-MC (10, 20, or 40 mg/kg). Administered intraperitoneally. | Rat | 6–8 | Precipitated, naltrexone (1 mg/kg, i.p.) on day 8 | Escalating morphine up to 140 mg/kg, s.c., for 7 days | Body weight, burying, diarrhea, flinching, grooming, teeth chattering, and wet dog shakes | 18-MC decreased body weight loss (40 mg/kg), burying (20 and 40 mg/kg), diarrhea (40 mg/kg), teeth chattering (20 and 40 mg/kg), and wet dog shakes (20 mg/kg). |
Schreiber et al. (2003) | Mianserin (25 mg/kg), trazodone (50 mg/kg), mianserin (25 mg/kg) + trazodone (50 mg/kg). Administered subcutaneously. | Mouse | >10 | Precipitated, naloxone (1 mg/kg, s.c.) | High morphine group: escalating morphine up to 160 mg/kg, s.c., by day 8; low morphine: escalating morphine up to 40 mg/kg, s.c., by day 8 | Grooming, jumping, and rearing | Mianserin (25 mg/kg), trazodone (50 mg/kg), and mainserin (25 mg/kg) + trazodone (50 mg/kg) combination reduced jumping, rearing, and grooming in both high and low morphine groups. |
Sharpe and Jaffe (1990) | Ibogaine (5, 10, 20, and 40 mg/kg). Administered subcutaneously. | Rat | 6 | Precipitated, naloxone (0.5 mg/kg, s.c.) on day 3 | Morphine (75 mg) subcutaneous implant for 3 days | Activity, grooming, lacrimation, mouth movement, paw shakes, penile licking, rhinorrhea, salivation, stretching, teeth chattering, wet dog shakes, and total withdrawal score | Ibogaine decreased grooming (10 mg/kg) and increased teeth chattering (5 mg/kg). |
Streel et al. (2005) | Ketamine (2.5 mg/kg), Midazolam (0.25 mg/kg). Administered intramuscularly | Rat | 10 | Precipitated, naloxone (1 mg/kg, s.c.) on day 3, administered three times (total daily dose 3 mg/kg, s.c.) | Escalating morphine up to 150 mg/kg, s.c., for 3 days | Abnormal posture, cheek tremors, defecation, escape attempts, head lift, jumping, mastication, salivation, sniffing, teeth chattering, urination, vocalization on touch, wet dog shakes, and total withdrawal score | Ketamine (2.5 mg/kg) decreased defecation, urination, and total withdrawal scores. Midazolam (0.25 mg/kg) decreased urination and total withdrawal scores. |