Cross-tolerance

Cross-tolerance is a phenomenon that occurs when someone who is tolerant to the effects of a certain drug also develops a tolerance to another drug. It often happens between two drugs with similar functions or effects – for example, acting on the same cell receptor or affecting the transmission of certain neurotransmitters. Cross-tolerance has been observed with pharmaceutical drugs such as anti-anxiety agents and illicit substances, and sometimes the two of them together. Oftentimes a person who uses one drug can be tolerant to a drug that has a completely different function. This phenomenon allows one to become tolerant to a drug that they have never even used before.

Antianxiety and sedative hypnotics
Exciting the GABA receptor produces an influx of Chloride ions, which hyperpolarizes it and makes it less likely to give rise to an action potential and decreases a neuron’s firing rate. The GABA receptor can also bind barbiturates and benzodiazepines. Barbiturates binding increases the binding of GABA and benzodiazepines maximizes the time the pore is open, both of these mechanisms allows for an influx of Chloride ions. When these drugs are taken together it is very dangerous because the effects of both are added up since they act on the same receptor, which is why when you have tolerance for one drug in the group you will most likely show cross-tolerance for the other drugs in the group.

Antipsychotic drugs
These drugs block dopamine receptors and can also block serotonin receptors

Antidepressants and Mood Stabilizers
A MAO inhibitor allows for more serotonin release by inhibiting enzymes that break down serotonin. Some of the other drugs block the reuptake transporter which takes some of the neurotransmitters back up, and disallows for the neurotransmitter to reach the next synapse.

Opioid analgesics
These drugs mimic three classes of endorphins, such as endomorphins, enkephalins, and dynorphins. All three of these classes each have their own receptor-mu, kappa, and delta. Opioids will bind to the receptor for the endorphin they are most alike. Heroin which is synthesized from morphine will also compete for the same receptor, but it is more dangerous because it can readily cross the blood-brain barrier unlike morphine.

Psychotropics
Amphetamine and cocaine block the reuptake of dopamine. Amphetamine also helps release dopamine from presynaptic membranes. Psychedelic drugs will either block or facilitate the transmission at its certain neurotransmitter receptor. Caffeine increases the metabolic activity of cells. It inhibits the enzyme which breaks down cAMP, allowing for further glucose production and therefore, more energy.

Drugs of Different Classifications
Sometimes cross-tolerance occurs between two drugs that do not share mechanisms of action or classification. For example, amphetamine and amphetamine-like stimulants have been shown to exhibit cross-tolerance with caffeine, and it is likely the mechanism of cross-tolerance involves the dopamine D(1) receptor. Amphetamines also have cross-tolerance with pseudoephedrine, as pseudoephedrine can block dopamine uptake in the same manner that amphetamines do, but less potently.

Alcohol is another substance that often cross-tolerates with other drugs. Findings of cross-tolerance with nicotine in animal models suggest that it is also possible in humans, and may explain why the two drugs are often used together. Numerous studies have also suggested the possibility of cross-tolerance between alcohol and cannabis.