Inhibitory effects of ibogaine on cocaine self-administration in rats

This animal study (n=56) examined the effects of single and repeated injections of ibogaine (40 mg/kg) on the cocaine self-administration model in rats and found that it inhibited addictive behaviors for 1-2 days or longer with additional weekly injections, even when ibogaine levels in the body were undetectable.

Abstract

“Introduction/Methods: In order to determine the potential anti-addictive properties of ibogaine, we used the cocaine self-administration model in rats.

Results: The results indicate that a single injection of ibogaine (40 mg/kg i.p.) produced a significant decrease of cocaine intake, which remained unaltered for more than 48 h. Since the half-life time of ibogaine is short, this might suggest the involvement of one or several active metabolites of ibogaine in cocaine intake. Repetitive administration of ibogaine on three consecutive days also induced a pronounced decrease of cocaine intake. However, a more prominent inhibitory effect on cocaine intake was observed in animals treated repeatedly with ibogaine (40 mg/kg i.p.), once each week for 3 consecutive weeks.

Discussion: These results indicate that ibogaine or its metabolite(s) is a long-lasting interruptor of cocaine dependence, which supports similar observations from uncontrolled clinical studies.”

Authors: Susanne Cappendijk & Michailo R. Dzoljic

Summary

1. Introduction

Recent animal studies indicate that ibogaine may significantly affect drug dependence phenomena such as drug withdrawal and intake of addictive drugs.

Ibogaine pretreatment decreases the intake of addictive drugs. Preliminary data were presented at a joint meeting of College on Problems of Drug Dependence, Inc. and International Narcotics Research Conference.

Ibogaine was shown to interrupt morphine, cocaine and amphetamine self-administration in rats for several days. It was also shown to attenuate alcohol and nicotine/tobacco dependency syndromes.

2.2. Operation procedure

All animals were anesthetized, surgically implanted with a chronic i.v. jugular catheter, and were deprived of food two days before the start of the experiments. A reversed 12-h light/dark cycle was maintained during the whole experiment.

2. 4. Test procedure

After 5-6 days of postoperative recovery, rats were connected to an infusion pump and tested for 6 weeks. The study of the effect of ibogaine began when the baseline rate of cocaine self-administration stabilized.

2.5. Experimental groups

In preliminary experiments, 80 mg/kg ibogaine caused severe locomotor disturbances, but 40 mg/kg ibogaine had less prominent and shorter lasting behavioural effects.

3.1.1. Behaviour

Ibogaine administration to cocaine-dependent rats induced stiffness of the hind legs, tremor, ataxia and hypersensitivity. The effect lasted for 30 min.

3.1.2. Cocaine intake

A single injection of 40 mg/kg ibogaine produced a significant depression of cocaine intake. The effect remained below the control level for the 24 h following.

A single dose of ibogaine (10-40 mg/kg i.p.) significantly decreased cocaine intake in rats, with a long-lasting (48 h) inhibition.

Ibogaine (40 mg/kg i.p., given once on each of three consecutive sessions) significantly decreased cocaine intake in rats when compared to the baseline intake and the vehicle-treated group.

Ibogaine administration on each of 3 consecutive days decreased cocaine intake. The effect lasted for 24 h after the third injection, but was not significantly different from a single injection.

3.2.2. Ibogaine administered at the beginning of each of 3 consecutive weeks

The baseline cocaine intake was not significantly affected by vehicle or ibogaine administration, but decreased significantly after the second and third administration.

Ibogaine (40 mg/kg i.p., given once at the beginning of each of 3 consecutive weeks) significantly decreased cocaine intake in rats when compared to the baseline intake and the vehicle-treated group.

4. Discussion

Ibogaine, given once a week, decreased cocaine intake in rats for 1-2 days. This effect might be due to an active and long-lasting metabolite of ibogaine or to irreversible interruption of the biological mechanism of cocaine dependence.

4.1. Disturbed locomotion

Ibogaine enhanced the amphetamine-induced increase of motor activity and might further affect the self-administration of cocaine, but the effect of ibogaine on motor activity lasted about 30 min and the anti-addictive effect remained for at least 2 days.

4.2. Dopaminergic system

Ibogaine has been shown to reduce the dopamine release in the nucleus accumbens, and this might explain its anti-addictive effect. However, the interaction between ibogaine and dopamine neurotransmission has not been shown conclusively.

4.3. Serotonergic system

The 5-HT uptake inhibitor, fluoxetine, attenuates cocaine self-administration in animals, and ibogaine inhibits the enzymic oxidation of 5-HT, but it is not known whether this effect exists in the CNS.

4.4. Central neuronal excitability

Ibogaine increases arousability, which might affect behaviour. Its proconvulsant effect lasts several hours, which is probably incompatible with self-administration behaviour, but it is less clear why cocaine intake is decreased in the absence of a proconvulsant EEG pattern.

Acknowledgements

This work was supported by the European Addiction Research Institute Rotterdam and contains software written by Mr. H. Van der Giessen.