Reversal tolerance

Himnan DJ Tolerance and reverse tolerance to toluene inhalation effects on open-field behavior. Pharmacol Biochem Behav 21 625-631, 1984 Hinman DJ Biphasic dose-response relationship for effects of toluene inhalation on locomotor activity. Pharmacol Biochem Behav 26 65-69, 1987 Hormes JT, Filley CM, Rosenberg NL Neurologic sequelae of chronic solvent vapor abuse. Neurology 36 698—702, 1986... 

The NMDA antagonist effects of ibogaine are significant in light of the fact that MK-801 also reduces tolerance to opiates and alcohol, and reverses tolerance to stimulants (Trujillo and Akil 1991 Khanna et al. 1993 Karler et al. 1989). 

S. Ye, Fuel cell anode structure for voltage reversal tolerance, US Patent 7608358, assigned to BDF IP Holdings Ltd. (Vancouber, BC, CA), October 27, 2009. 

Hoffmann, O. and Wiesenfeld-Hallin, Z. Dextromethorphan potentiates morphine antinociception, but does not reverse tolerance in rats, Neuroreport 1996, 7, 838-840. 

Repeated intoxication with cocaine may produce complex adaptations of the dopamine neuronal system, including both tolerance and, indeed, the opposite phenomenon, called sensitization or reverse tolerance. One example of reverse tolerance may be what happens to some abusers on repeated intoxication with cocaine at doses that previously only induced euphoria. In these cases, cocaine causes a behavioral... 

In addition to the acute intoxicating effects and the chronic reverse tolerance effects of cocaine, all of which are mediated by increasing dopamine levels due to its release from dopamine synapses, there are also longer-term effects of cocaine, possibly due to other, more traditional desensitization types of adaptations of dopamine receptors. As abusers use cocaine for longer and longer periods of time, their dopamine receptors become desensitized (down-regulated) as they adapt to chronic... 

Repeated cocaine use can lead to reverse tolerance, such as acute paranoid psychosis. 

Tolerance to the effects of marijuana clearly exist even though chronic users have described a reversed tolerance and claim that smaller doses of the drug are necessary to produce the desired effects. This effect is probably related to the manner of use and the expectations of the user. Chronic, high-dose cannabis users may experience an abstinence or withdrawal syndrome on abrupt discontinuation of use. Signs and symptoms include irritability, restlessness, nervousness, weight loss, insomnia, and rapid eye movement (REM) rebound. Onset of this syndrome is several hours after the last dose, and it lasts 4 to 5 d. Because withdrawal is not life-threatening, treatment involves little more than supportive therapy with short-term, low doses of benzodiazepines. 

A "reverse tolerance" has also been described, whereby an alcoholic taking a small quantity of alcohol may become intoxicated, aggressive, and antisocial. This occurs in those who have brain or liver damage and therefore show an enhanced sensitivity to the disinhibiting actions of the drug or a decreased metabolism. 

Reverse tolerance, or sensation, can occur with all the psychostimulants, and may be partly related to enhanced mesolimbic forebrain dopaminergic function. Such increased sensitivity to the effects of these drugs need not depend on the drugs being given daily. The stereotyped behaviour seen in amphetamine abusers may be attributed to the increased activity of the striatal dopaminergic system. 

In other studies, volunteers previously dependent on amphetamines were dosed to a level at which amfetamine psychosis was produced, in order to examine the mechanism of action and pharmacokinetics of amfetamine and its possible relation to schizophrenia (64,65). Psychosis was induced by moderately high doses of amfetamine and the psychotic symptoms were often a replication of the chronic amfetamine psychosis, raising the question of whether the establishment of chronic stimulant psychosis leaves residual vulnerability to psychosis precipitated by stimulants. The mechanism might be similar to that which operates in the reverse tolerance that has been seen in experimental animals (66). In some cases an underlying psychosis can be precipitated an increase in schizophrenic symptoms (SED-8, 12) was observed in 17 actively ill schizophrenic patients after a single injection of amfetamine. 

Knights S etal, 2001a, Fuel Cell Anode Structure for Voltage Reversal Tolerance. WO 01/15247. 

Reverse tolerance Increased. sensitivity to a drug with repeated use of it (Chapter 5). 

Cocaine is a psychotomimetic drug, sometimes even at system-ically nontoxic doses. A kindling phenomenon has been described with cocaine in which neuronal function becomes altered with each dose of the drug. This causes a type of reverse tolerance with increased receptor sensitivity to cocaine, and psychosis may be caused by doses that formerly did not cause psychosis. The toxic psychosis is characterized by auditory, visual, and frequently tactile hallucinations, paranoid thinking, and looseness of associations. The psychosis is qualitatively very similar to a paranoid schizophrenic psychosis. ... 

Chronic cannabinoid administration may cause either tolerance or reverse tolerance. After 3 days of treatment, tolerance developed to the MES effects of A -THC and CBD in mice [183]. After 22 days of A -THC, tolerance developed to its anti-convulsant effects at 6 Hz, while with CBD an anticonvulsant reverse-tolerance occurred at 60 Hz. Apparently, CBD is superior to A -THC not only in being relatively free of psychotropic effects but also in inducing less anticonvulsant tolerance after prolonged use [184]. 

On topical application in mineral oil, a somewhat different order of activity was recorded A6-THC > A -THC 3 6a-OH-A -THC > CBD > 7-OH-A -THC > 6,7-dihydroxy-A -THC > 7-OH-A6-THC > 60-OH-A -THC [214], These results do not follow the well-established cannabimimetic SAR. This conclusion is strengthened by the recent observation that the naturally occurring cannabigerol (48), which is not cannabimimetic, reduces IOP in the cat and moreover showed reverse tolerance (in being more effective after chronic administration than in acute one) [215]. 

Studies of tolerance have been quite contradictory and scarce in both rabbits and humans [202], and in two reports from the laboratory of Colasanti a reverse tolerance was seen in cats [206,215]. It is therefore difficult to draw any conclusions at this point regarding the development of tolerance to the lowering of IOP by cannabinoids until more systematic, well-controlled studies become available. 

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