In this Part II psychiatric disorders coexisting with organic diseases are discussed. "Comorbidity phenomenon" defines the not univocal interrelation between medical illnesses and psychiatric disorders, each other negatively influencing morbidity and mortality. Most severe psychiatric disorders, such as schizophrenia, bipolar disorder and depression, show increased prevalence of cardiovascular disease, related to poverty, use of psychotropic medication, and higher rate of preventable risk factors such as smoking, addiction, poor diet and lack of exercise. Moreover, psychiatric and organic disorders can develop together in different conditions of toxic substance and prescription drug use or abuse, especially in the emergency setting population. Different combinations with mutual interaction of psychiatric disorders and substance use disorders are defined by the so called "dual diagnosis". The hypotheses that attempt to explain the psychiatric disorders and substance abuse relationship are examined: (1) common risk factors; (2) psychiatric disorders precipitated by substance use; (3) psychiatric disorders precipitating substance use (self-medication hypothesis); and (4) synergistic interaction. Diagnostic and therapeutic difficulty concerning the problem of dual diagnosis, and legal implications, are also discussed. Substance induced psychiatric and organic symptoms can occur both in the intoxication and withdrawal state. Since ancient history, humans selected indigene psychotropic plants for recreational, medicinal, doping or spiritual purpose. After the isolation of active principles or their chemical synthesis, higher blood concentrations reached predispose to substance use, abuse and dependence. Abuse substances have specific molecular targets and very different acute mechanisms of action, mainly involving dopaminergic and serotoninergic systems, but finally converging on the brain's reward pathways, increasing dopamine in nucleus accumbens. The most common substances producing an addiction status may be assembled in depressants (alcohol, benzodiazepines, opiates), stimulants (cocaine, amphetamines, nicotine, caffeine, modafinil), hallucinogens (mescaline, LSD, ecstasy) and other substances (cannabis, dissociatives, inhalants). Anxiety disorders can occur in intoxication by stimulants, as well as in withdrawal syndrome, both by stimulants and sedatives. Substance induced mood disorders and psychotic symptoms are as much frequent conditions in ED, and the recognition of associated organic symptoms may allow to achieve diagnosis. Finally, psychiatric and organic symptoms may be caused by prescription and doping medications, either as a direct effect or after withdrawal. Adverse drug reactions can be divided in type A, dose dependent and predictable, including psychotropic drugs and hormones; and type B, dose independent and unpredictable, usually including non psychotropic drugs, more commonly included being cardiovascular, antibiotics, anti-inflammatory and antineoplastic medications.