Toxic Substances and Drugs

Substance-induced psychosis (commonly known as toxic psychosis) is a form of substance use disorder where psychosis can be attributed to substance use. It is a psychosis that results from the poisonous effects of chemicals or drugs, including those produced by the body itself. Various psychoactive substances have been implicated in causing or worsening psychosis in users.

Effects of Psychosis Main article: Psychosis Psychosis manifests as disorientation and visual (and/or haptic) hallucinations.[1] It is a state in which a person's mental capacity to recognize reality, communicate, and relate to others is impaired, thus interfering with the capacity to deal with life demands. While there are many types of psychosis, substance-induced psychosis can be pinpointed to specific chemicals.[2]

Substances Psychotic states may occur after using a variety of legal and illegal substances. Usually such states are temporary and reversible, with fluoroquinolone-induced psychosis being a notable exception. Drugs whose use, abuse, or withdrawal are implicated in psychosis include the following:

ICD-10 (International Classification of Diseases) 

F10.5 alcohol:[3][4][5] Alcohol is a common cause of psychotic disorders or episodes, which may occur through acute intoxication, chronic alcoholism, withdrawal, exacerbation of existing disorders, or acute idiosyncratic reactions.[6] Research has shown that alcohol abuse causes an 8-fold increased risk of psychotic disorders in men and a 3 fold increased risk of psychotic disorders in women.[7][8] While the vast majority of cases are acute and resolve fairly quickly upon treatment and/or abstinence, they can occasionally become chronic and persistent.[6] Alcoholic psychosis is sometimes misdiagnosed as another mental illness such as schizophrenia.[9]



F12.5 cannabinoid: Some studies indicate that cannabis, especially certain strains containing large proportions of THC and low proportions of CBD,[10] may lower the threshold for psychosis, and thus help to trigger full-blown psychosis in some people.[11] Recent studies have found an increase in risk for psychosis in cannabis users.[12] It is not clear whether this is a causal link; it is possible that cannabis use only increases the risk of psychosis in people already predisposed to it.



F13.5 sedatives/hypnotics (barbiturates;[13][14] benzodiazepines[15][16][17]): It is also important to this topic to understand the paradoxical effects of some sedative drugs.[18] Serious complications can occur in conjunction with the use of sedatives creating the opposite effect as to that intended. Malcolm Lader at the Institute of Psychiatry in

London estimates the incidence of these adverse reactions at about 5%, even in shortterm use of the drugs.[19] The paradoxical reactions may consist of depression, with or without suicidal tendencies, phobias, aggressiveness, violent behavior and symptoms sometimes misdiagnosed as psychosis.[20][21] However, psychosis is more commonly related to the benzodiazepine withdrawal syndrome.[22] 

F14.5 cocaine[23]



F15.5 other stimulants: amphetamines;[24] methamphetamine;[24] methylphenidate.[24] See also stimulant psychosis.



F16.5 hallucinogens (LSD and others)

The code F11.5 is reserved for opioid-induced psychosis, and F17.5 is reserved for tobaccoinduced psychosis, but neither substance is traditionally associated with the induction of psychosis. The code F15.5 also includes caffeine-induced psychosis, despite not being specifically listed in the DSM-IV. However, there is evidence that caffeine, in extreme acute doses or when severely abused for long periods of time, may induce psychosis.[25][26]

Other 

Fluoroquinolone drugs, fluoroquinolone use has been linked to serious cases of toxic psychosis that have been reported to be irreversible and permanent, see adverse effects of fluoroquinolones[27][28][29][30][31][32][33][34] The related quinoline derivative mefloquine (Lariam) has also been associated with psychosis.[35][36]



some over-the-counter drugs, including: o Dextromethorphan (DXM) at high doses.[37][38] o Certain antihistamines at high doses.[39][40][41][42] o Cold Medications[43] (i.e. containing Phenylpropanolamine, or PPA)



prescription drugs: o Prednisone and other corticosteroids[44] o Isotretinoin[45] o Anticholinergic drugs 

atropine[46][47]



scopolamine[48]

o antidepressants[49] o L-dopa[50] o antiepileptics[51] 

antipsychotics, in an idiosyncratic reaction



Other illegal drugs (not listed above), including: o MDMA (ecstasy)[52] o Phencyclidine (PCP)[53] o Ketamine



Synthetic research chemicals used recreationally, including: o JWH-018 and some other synthetic cannabinoids, or mixtures containing them (e.g. "Spice", "Kronic", "MNG" or "Mr. Nice Guy", "Relaxinol", etc.).[54] Various "JWH-XXX" compounds in "Spice" or "Incense" have also been found and have been found to cause psychosis in some people.[55][56] o Mephedrone and related amphetamine-like drugs sold as "bath salts" or "plant food".[57]



Plants o Hawaiian baby woodrose (contains ergine) o Morning glory seeds (contains ergine) o Jimson weed[58] (Datura, angel's trumpet, thorn apple) o Belladonna (deadly nightshade) o Salvia divinorum[59]



Volatile solvents and gases (inhalants) o Toluene,[60][61] found in glue, paint, thinner, etc. See also toluene toxicity.

o Butane[62] o Gasoline (petrol),[63]

Lethal dose From Wikipedia, the free encyclopedia

A lethal dose (LD) is an indication of the lethality of a given substance[1][2] or type of radiation. Because resistance varies from one individual to another, the 'lethal dose' represents a dose (usually recorded as dose per kilogram of subject body weight) at which a given percentage of subjects will die. The LD may be based on the standard person concept, a theoretical individual that has perfectly "normal" characteristics, and thus not apply to all sub-populations. Lethal doses are usually expressed as median lethal dose (LD-50), the point where 50% of test subjects exposed would die, in the units of mg/kg body weight. For gases and aerosols, lethal concentration (mg/m³ or ppm, parts per million) is the analogous concept, although this also depends on the duration of exposure, which has to be included in the definition. The lowest known lethal dose, derived from an individual case of poisoning, is abbreviated LCLo. LD values for humans are best estimated by extrapolating results from human cell cultures. One outdated form of extrapolation involves measuring LD on animals like mice or dogs, converting to dosage per kilogram of biomass, and extrapolating to human norms. The degree of error from animal-extrapolated LD values is very large. The biology of test animals differs in important aspects to that of humans. For instance, mouse tissue is approximately fifty times less responsive than human tissue to the venom of the Sydney funnel-web spider. The square-cube law also complicates the scaling relationships involved. Researchers are now shifting away from animalbased LD measurements. The U.S. Food and Drug Administration has begun to approve more reliable non-animal methods in response to research cruelty concerns and the lack of validity/sensitivity of animal tests as they relate to humans.[3][4] "LD50" redirects here. For other uses, see LD50 (disambiguation). In toxicology, the median lethal dose, LD50 (abbreviation for "lethal dose, 50%"), LC50 (lethal concentration, 50%) or LCt50 (lethal concentration and time) of a toxin, radiation, or pathogen is the dose required to kill half the members of a tested population after a specified test duration.[1] LD50 figures are frequently used as a general indicator of a substance's acute toxicity. A lower LD50 is indicative of increased toxicity. The test was created by J.W. Trevan in 1927.[2] The term semilethal dose is occasionally used with the same meaning, in particular in translations from non-English-language texts, but can also refer to a sublethal dose; because of this ambiguity, it is usually avoided. LD50 is usually determined by tests on animals such as laboratory mice. In 2011 the US Food and Drug

Administration approved alternative methods to LD50 for testing the cosmetic drug BOTOX without animal tests.[3][4] Examples

NOTE: Comparing substances (especially drugs) to each other by LD50 can be misleading in many cases due (in part) to differences in effective dose (ED50). Therefore, it is more useful to compare such substances by therapeutic index, which is simply the ratio of LD50 to ED50. The following examples are listed in reference to LD50 values, in descending order, and accompanied by LC50 values, {bracketed}, when appropriate.

Substance

Animal, Route

LD50 {LC50}

LD50 : g/kg {LC50 : Refere g/L} nce standardi zed

Water

rat, oral

>90g/kg

>90

[8]

Sucrose (table sugar)

rat, oral

29,700 mg/k 29.7 g

[9]

Monosodium glutamate (MSG) rat, oral

16,600 mg/k 16.6 g

[10]

Vitamin C (ascorbic acid)

rat, oral

11,900 mg/k 11.9 g

[11]

Urea

rat, oral

8,471 mg/kg 11.5

[12]

Cyanuric acid

rat, oral

7,700 mg/kg 7.7

[13]

cadmium sulfide

rat, oral

7,080 mg/kg 7.08

[14]

Grain alcohol (ethanol)

rat, oral

7,060 mg/kg 7.06

[15]

sodium isopropyl methylphosphonic acid (IMPA, rat, oral metabolite of sarin)

6,860 mg/kg 6.86

[16]

Melamine

rat, oral

6,000 mg/kg 6

[13]

Melamine cyanurate

rat, oral

4,100 mg/kg 4.1

[13]

Sodium molybdate

rat, oral

4,000 mg/kg 4

[17]

Substance

Animal, Route

LD50 {LC50}

LD50 : g/kg {LC50 : Refere g/L} nce standardi zed

3,000 mg/kg 3

[18]

Paracetamol (acetaminophen) rat, oral

1,944 mg/kg 1.944

[19]

Delta-9-tetrahydrocannabinol rat, oral (THC)

1,270 mg/kg 1.270

[20]

Metallic Arsenic

rat, oral

763 mg/kg

0.763

[21]

Alkyl dimethyl benzalkonium chloride (ADBAC)

rat, oral fish, immersion aq. invertebrates, imm.

304.5 mg/kg {0.28 mg/L} {0.059 mg/L }

0.3045 {0.00028} [22] {0.000059 }

Coumarin (benzopyrone, from Cinnamomum aromaticum rat, oral and other plants)

293 mg/kg

0.293

[23]

Aspirin (acetylsalicylic acid)

rat, oral

200 mg/kg

0.2

[24]

Caffeine

rat, oral

192 mg/kg

0.192

[25]

Arsenic trisulfide

rat, oral

185–6,400 m 0.185 g/kg

[26]

Sodium nitrite

rat, oral

180 mg/kg

0.18

[27]

uranyl acetate dihydrate

mouse, oral

136 mg/kg

0.136

[28]

Bisoprolol

mouse, oral

100 mg/kg

0.1

[29]

Cobalt(II) chloride

rat, oral

80 mg/kg

0.08

[30]

Cadmium oxide

rat, oral

72 mg/kg

0.072

[31]

Sodium fluoride

rat, oral

52 mg/kg

0.052

[32]

Pentaborane

human, oral