Psychopharmacology of REM Sleep and Dreams
All the mood altering drugs appear to profoundly alter REM sleep
Posted Dec 04, 2011
All the most commonly prescribed drugs for mental and emotional disorders affect dreams—typically via their effects on REM sleep. Under healthy conditions REM sleep ‘turns-on' when activity levels of the biogenic amines (e.g. noradrenaline) decrease and activity levels of acetylcholine increase. It is therefore not surprising to find that drugs that increase cholinergic activity generally tend to increase REM sleep and dream recall.
People on the nicotine patch, for example, often report to me that they are dreaming more and that their dreams have become vivid and intense. Currently available treatments for Alzheimer's Disease (donepezil, rivastigmine, galantamine and memantine) are all fundamentally designed to increase forebrain cholinergic activity. All of these drugs have been associated with reports of increased dream recall and more vivid dreaming.
Some drugs can influence REM sleep and dreaming indirectly via their effects on NREM sleep-especially slow wave sleep (SWS). To the extent that SWS and REM mutually antagonize or inhibit one another's physiologies suppressing one should lead to the dis-inhibition of the other. Most currently prescribed hypnotics, such as the benzodiazepines and Z-drugs (e.g., Zolpidem/Ambien; Eszopiclone/Lunesta) suppress SWS.
If suppression of SWS leads to a dis-inhibition of REM, there should be some evidence of enhanced REM sleep and enhanced dream recall in persons taking these medications. There is. Most people on these drugs do report enhanced dreams.
Many of the mind-altering, and most of the addicting drugs are associated with REM suppression during use and REM dis-inhbition during withdrawal. Many sleep scientists believe that the nightmares and hallucinations associated with acute withdrawal states are related to this dis-inhibited REM state.
For example, ingestion of cocaine increases wakefulness and suppresses REM sleep. Similarly, ingestion of 3,4-methylenedioxymethamphetamine (MDMA; "ecstasy") increases arousal/wakefulness and suppresses REM. LSD ingestion alters sertoninergic transmission and is associated with REM dis-inhibition. For both cocaine and ecstasy withdrawal people report very unpleasant and intense dreams.
Alcohol too is associated with REM suppression during the intoxicated state and profound REM dis-inhibition during the withdrawal state. In extreme cases REM makes up 100% of sleep and becomes so disorganized during alcohol withdrawal that the patient suffers delirium tremens. Here the patient appears to be in extreme fear and is persistently hallucinatory. "DTs" are one of the most horrifying things I have ever witnessed a patient undergo. The patient is literally stuck in a nightmare for days on end.
Another class of drugs which affect REM sleep and dreams are the anti-depressants, particularly the selective serotonin reuptake blockers (e.g., fluoxetine, paroxetine etc). These drugs increase serotonergic and to a lesser extent noradrenergic activity levels in the forebrain. Most of these drugs affect one or more aspects of REM sleep. For example, prolonged use causes the eye movements normally associated with REM to escape the temporal bounds of REM sleep and appear in other forms of sleep or during the waking period.
Patients on these SSRI drugs typically report intense dreams that last all night long. Citalopram may be the exception here but all the data are not in yet. Monoamine Oxidase Inhibitors (MAOI's), another class of agents used against mood disorder, block the activity of the enzyme, monoamine oxidase, which normally breaks down norepinephrine and serotonin in the synaptic cleft. Some patients given MAOI's report loss of the ability to dream for months on end.
This quick survey of pharmacological agents that influence REM sleep and dreaming is generally consistent with current animal models of the neurochemistry of REM sleep but there are many unanswered questions:
How does REM dis-inhibition after REM suppression contribute to hallucinatory and psychotic states seen in withdrawal from addicting substances?
To what extent is the improved cognition seen in patients with dementia who are given cholinergic agents due to enhanced REM or normalization of REM?
How is the timecourse of REM suppression related to symptom remission in patients with depression who are taking SSRIs?
These and many other related questions still need study if we are to understand REM sleep and the array of mental disorders associated with REM dysfunction.
Hobson, J.A. The dream drug store. (MIT Press, Cambridge, MA 2001)